Vulvar Varicosities in an Adolescent Girl with Morbid Obesity: A Case Report.

Vulvar varicosities in nonpregnant females, either isolated or as a part of the pelvic congestion syndrome, are rare. We present a case of an adolescent girl with morbid obesity with bilateral bluish protrusions on the labia minora, as an incidental finding, that coincided with her excessive weight gain. The adolescent underwent thorough clinical examination, doppler ultrasound, contrast venography and varicography, and magnetic resonance angiography to rule out alternative diagnoses. Imaging results confirmed the presence of large venous lakes. Venous drainage to the internal iliac vein and connections with the long saphenous vein were delineated. Incompetence, dilatation, or reflux of ovarian or internal iliac veins, or their main tributaries, were not noted. Since the adolescent was asymptomatic and other pathologies, such as vascular malformations or hemangiomas were excluded, she was managed conservatively with counseling about lifestyle modification and weight reduction. This is only the third reported case of vulvar venous varicosities in adolescents. Female sex, along with obesity, are known risk factors for varicose vein formation; however, the pathogenesis is not fully understood. Additional research is needed to elucidate the role of excess adipose tissue in the pathophysiology of vulvar varicose veins and to optimize diagnostic workup and management in adolescence.

Acceptability of Self-Sampling for Human Papillomavirus-Based Cervical Cancer Screening.

Background: Human papillomavirus (HPV)-DNA testing combined with self-sampling could increase cervical cancer screening effectiveness, utilizing a sensitive screening modality and an easy sampling method with minimal pain or discomfort. Self-sampling acceptability, though, is pivotal. Materials and Methods: This study is a nested cross-sectional survey within GRECOSELF, a cross-sectional study on HPV-based screening with self-sampling, aiming at investigating self-sampling acceptability among Greek women residing in rural areas, and the factors affecting it. Women between 25 and 60 years old were recruited by midwives participating in a nationwide midwifery network. Participants, after self-sampling, filled out a questionnaire with three sections, one regarding demographic characteristics, a second with questions pertaining to the participants' cervical cancer screening history, and a third with questions regarding the self-sampling process per se. Results: The sample included 13,111 women. Most participants (67.9%), including those screened or not in the past, would prefer self-sampling if assured that the results are not inferior to standard testing. Discomfort or pain during self-sampling was absent or minimal in 97.1% and 96.5% of the cases, respectively, and 74.4% of the women felt adequately confident that they followed the instructions correctly. Women mostly preferred self-sampling at home compared with health care facilities. Pain and discomfort during the procedure, although rare, were significant factors against acceptance. Most of the women reporting a negative impression had a negative experience with conventional sampling in the past. Conclusion: Self-sampling is highly acceptable. Acceptance can be further improved with proper communication of the process and its noninferiority compared with conventional screening.

Implementation of HPV-based Cervical Cancer Screening Combined with Self-sampling Using a Midwifery Network Across Rural Greece: The GRECOSELF Study.

Self-sampling for human papillomavirus (HPV) testing is an alternative to physician sampling particularly for cervical cancer screening nonattenders. The GRECOSELF study is a nationwide observational cross-sectional study aiming to suggest a way to implement HPV-DNA testing in conjunction with self-sampling for cervical cancer screening in Greece, utilizing a midwifery network. Women residing in remote areas of Greece were approached by midwives, of a nationwide network, and were provided with a self-collection kit (dry swab) for cervicovaginal sampling and asked to answer a questionnaire about their cervical cancer screening history. Each sample was tested for high-risk (hr) HPV with the Cobas HPV test. HrHPV-Positive women were referred to undergo colposcopy and, if needed, treatment according to colposcopy/biopsy results. Between May 2016 and November 2018, 13,111 women were recruited. Of these, 12,787 women gave valid answers in the study questionnaire and had valid HPV-DNA results; hrHPV prevalence was 8.3%; high-grade cervical/vaginal disease or cancer prevalence was 0.6%. HrHPV positivity rate decreased with age from 20.7% for women aged 25-29 years to 5.1% for women aged 50-60 years. Positive predictive value for hrHPV testing and for HPV16/18 genotyping ranged from 5.0% to 11.6% and from 11.8% to 27.0%, respectively, in different age groups. Compliance to colposcopy referral rate ranged from 68.6% (for women 25-29) to 76.3% (for women 40-49). For women residing in remote areas of Greece, the detection of hrHPV DNA with the Cobas HPV test, on self-collected cervicovaginal samples using dry cotton swabs, which are provided by visiting midwives, is a promising method for cervical cancer secondary prevention.

Postpartum nephrotic syndrome related to new onset of systemic lupus erythematosus: A case report.

Postpartum nephrotic syndrome in a pregnant woman with rheumatoid arthritis in long-standing remission is rare. Systemic lupus erythematosus can remain undiagnosed, especially in the absence of clinical manifestations. We present the case of a 34-year-old woman (gravida 2, para 1) who underwent a lower-segment cesarean section at 34 weeks and 6 days of gestation because she had developed preeclampsia and nephrotic syndrome. The concomitant presence of significant hypoproteinemia, hypoalbuminemia, uremia, elevated creatinine serum levels, hyperuricemia and hypertriglyceridemia is indicative of impaired renal function and nephrotic syndrome. This woman was diagnosed with systemic lupus erythematosus nephritis. It is imperative for clinicians to investigate the exact pathophysiological causes of nephrotic syndrome with onset in the puerperium and implement the appropriate therapeutic regimens.

Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions.

Human papillomavirus (HPV) infection alone is not sufficient to explain the development of cervical cancer. Genetic variants have been linked to the development of precancerous lesions and cervical cancer. In this study, we aimed to evaluate the association of 10 single nucleotide polymorphisms (SNPs) of the Fas cell surface death receptor (FAS), trinucleotide repeat containing 6C (TNRC6C), transmembrane channel like 8 (TMC8), DNA meiotic recombinase 1 (DMC1), deoxyuridine triphosphatase (DUT), sulfatase 1 (SULF1), 2'-5-oligoadenylate synthetase 3 (OAS3), general transcription factor IIH subunit 4 (GTF2H4) and interferon gamma (IFNG) genes with susceptibility to precancerous lesions and cervical cancer. In total, 608 female participants, consisting of 199 patients with persistent low-grade precancerous lesions (CIN1), 100 with high-grade precancerous lesions (CIN2/3), 17 patients with cervical cancer and 292 healthy controls, were enrolled in this study. SNPs were tested for associations with each of the above-mentioned cervical group lesions or when considering an overall patient group. A significant difference for rs4737999 was observed between the controls and the overall patient group considering the recessive mode of inheritance [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.24-0.96; P=0.033]. This effect was even stronger on the risk of CIN1 lesions. Carriers of the rs4737999 AA genotype were almost 3-fold less likely of having low grade lesions compared to the other genotypes. On the whole, this study provides evidence of an influence of the SULF1 gene rs4737999 SNP in the development of precancerous lesions/cervical cancer.

Intrauterine HPV transmission: a systematic review of the literature.

PURPOSE: To evaluate the percentage of intrauterine vertical human papillomavirus (HPV) transmission among HPV-positive mothers and the relative risk of intrauterine vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women. METHODS: This systematic review was made according to the PRISMA statement. We searched PubMed and Scopus and the final articles were selected by two reviewers. Data from the selected articles were plotted, and the pooled percentage of antenatal vertical HPV transmission among HPV-positive mothers as well as the pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women were calculated. RESULTS: 9 studies including 421 HPV-positive mothers and their offsprings were selected from 434 potential papers. Following meta-analysis, the pooled percentage of antenatal vertical HPV transmission was 4.936% (95% CI 1.651-9.849), with moderate heterogeneity between the studies (I2 = 72.22%). The pooled relative risk of antenatal vertical HPV transmission between cesarean and vaginal delivery among HPV-positive women was 0.912, with no statistical significance (95% CI 0.226-3.674) and homogeneity between the studies (I2 = 24.48%).

The eminent gynaecologist Richard Wesley TeLinde (1894- 1989) and his contribution to diagnosis of cervical cancer.

At the beginning of the 20th century, the relation of carcinoma in situ of the cervix to the invasive cancer was poorly understood, resulting in misdiagnosis of the disease and inappropriate treatment. The work of Richard Wesley TeLinde, chairman of Gynaecology at Johns Hopkins University for almost 21 years, contributed to delineate the diagnosis of cervical carcinoma, providing suggestive evidence that carcinoma in situ often precedes invasive cervical cancer.

Considerations Regarding Embryo Culture Conditions: From Media to Epigenetics.

There are numerous reports on embryo culture media and conditions in the laboratory, as the subject is multifaceted and complex, reflecting the variation in practice. In this scoping review, we attempt to approach the topic of culture media and conditions from the practitioners' perspective aiming to highlight, in a comprehensive fashion, important aspects regarding the options available, introduce points of debate and controversy, while maintaining the viewpoint of the practicing embryologist's concerns.

Cervical cancer in the work of the unconventional Samuel Pozzi (1846-1918), pioneer of modern gynaecology.

Advocate of Lister's antiseptic techniques, promoter of anesthesia, professor of the first chair of gynaecology in Medical School of Paris, academician, successful politician, art collector, friend and lover of the famous, Samuel Pozzi lived a fascinating life. His book "Treatise of clinical and surgical gynaecology" published in 1890 became the gold standard in medical practice while his approach in the treatment of cervical cancer, including cases of pregnant women, remained in vogue for almost fifty years.

Abnormal Uterine Bleeding including coagulopathies and other menstrual disorders.

Abnormal Uterine Bleeding (AUB) is a frequent cause of visits to the emergency department and a major reason for concern among adolescents and their families. The most common cause of AUB, in otherwise healthy adolescents, is ovulatory dysfunction, although 5-36% of adolescents who present with heavy menstrual bleeding, have an underlying bleeding disorder (BD). The most common form of BDs is von Willebrand Disease, reflecting 13% of adolescents with AUB. Management of AUB depends on the underlying etiology, the bleeding severity, as well as the need for hospitalization. Treatment of adolescents with an underlying coagulopathy depends on the severity of the BD, while therapeutic interventions are summarized in supportive measures, hormonal treatments (e.g. Combined Oral Contraceptives), non-hormonal treatments (e.g. tranexamic acid and desmopressin), surgical options (e.g. dilatation & curettage) and treatment options in specific conditions.

Assessment of bone metabolism and biomechanical properties of the femur, following treatment with anastrozole and letrozole in an experimental model of menopause.

The aim of the present study was to investigate the impact of anastrozole and letrozole supplementation following surgically induced menopause on bone metabolism and biomechanical properties. A total of 45 Wistar rats underwent ovariectomy and were then randomly allocated to receive no treatment, anastrozole or letrozole. At 2 and 4 months following the initiation of the present study, the serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were determined, and the animals were sacrificed at the end of the 4-month period to assess the biomechanical properties of the femoral bones. The applied force and the deflection of the central section were recorded during the test. Taking advantage of these quantities, the fracture force, the stiffness of the bone and the energy absorbed until fracture were determined. At 2 months following the initiation of the experimental protocol, the mean OPG levels were significantly increased in the control group compared with the anastrozole-treated group (P<0.01). Similarly, RANKL levels were significantly increased in the control rats compared with the anastrozole-treated animals (P<0.001) and animals that received letrozole (P<0.05). Notably, these trends were not observed at the end of the experiment (4 months). A biomechanical study of the femoral bones revealed significantly decreased stiffness among animals that received anastrozole (P<0.05) and letrozole (P<0.01) compared with their control counterparts. The results of the present study indicate that treatment with anastrozole and letrozole significantly increases the levels of OPG and RANKL in bone, an effect that appears to be directly associated with the biomechanical properties of bones.

Correlation of serum anti-Müllerian hormone levels with positive in vitro fertilization outcome using a short agonist protocol.

OBJECTIVE: We examined the predictive ability of anti-Müllerian hormone (AMH) for clinical pregnancy in women who underwent in vitro fertilization (IVF) cycles in a short agonist protocol. DESIGN: This is a retrospective cohort study of 222 women undergoing their first IVF attempt between June 2010 and March 2016. Multivariate logistic regression analysis was performed to evaluate the independent associations between clinical pregnancy and its possible predictors. RESULTS: 14.9% of cycles were cancelled, >3 oocytes were retrieved in 55.4% of cycles and embryo transfer was performed in 70.7% of cases. Live birth was the final outcome in 19.8% of subjects, miscarriage occurred in 4.1%, whereas no pregnancy occurred in the remaining 76.1% of the study sample. The number of oocytes, number of embryos, embryo transfer rate and pregnancy rates were positively associated with serum AMH concentrations (p <0.001, for each association). When analyzed by age quartiles, the overall association between AMH and clinical pregnancy rates was evident across all age strata. CONCLUSIONS: Serum AMH levels are a strong predictive marker of clinical pregnancy in women undergoing a short agonist IVF protocol. There is also a strong association with cancellation rate, number of oocytes retrieved, poor response (≤3 oocytes), number of embryos, embryo transfer rate and live birth rates.

The role of total body fat mass and trunk fat mass, combined with other endocrine factors, in menstrual recovery and psychopathology of adolescents with Anorexia Nervosa.

OBJECTIVE: To determine the threshold of total body and trunk fat mass required for menstrual recovery and to assess the impact of body composition in psychopathology of adolescents with Anorexia Nervosa (AN). METHODS: Prospective study of 60 adolescents presented with secondary amenorrhea and diagnosed with AN. Anthropometrics, body composition by dual-energy X-ray absorptiometry, hormonal studies and responses to mental health screens (EAT-26), were obtained at the beginning and at complete weight restoration, in all adolescents, independently of menstrual recovery (Group A) or not (Group B). RESULTS: At weight restoration, Group A total body fat mass, trunk fat mass, and trunk/extremities fat ratio were significantly higher (p < .001) than Group B. Menstruation was expected in 20% of total body fat mass and 20% of trunk fat mass (% of total trunk tissue). At time of menstrual recovery, total body fat mass (%) and trunk fat mass (%) were significantly negatively correlated with EAT-26 (r = -0.363, p = .032) and (r = -0.416, p = .013), respectively, while an increase of 0.40% of trunk fat mass (%) lowers EAT-26 by one unit. DISCUSSION: Trunk fat mass distribution can positively influence psychopathology of adolescents with AN.

Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence: an update.

Abnormal uterine bleeding (AUB) is a frequent reason for concern between adolescents. The most common cause of AUB in these girls, when other pathologies have been excluded, is dysfunctional uterine bleeding (DUB). The aim of this review is to assess the role of DUB as an early symptom of polycystic ovarian syndrome (PCOS) diagnosis later in life. A review of the literature was performed, using Pubmed and Medline as primary databases, regarding the correlation between DUB cases early after menarche and PCOS diagnosis in the future. The most plausible pathophysiological mechanism in the vast majority of DUB cases is the immaturity of hypothalamic pituitary ovarian (HPO) axis. Similarities between normal changes in puberty and PCOS later in life such as: increased ovarian and adrenal steroidogenesis, hyperpulsatile gonadotropin secretion, hyperinsulinemia and insulin resistance, anovulation and therefore menstrual irregularity, including DUB, have been noted in several studies. Anovulation, which can be first expressed as DUB at perimenarchal age, may persist and strengthen PCOS diagnostic criteria sometime during lifetime. Thorough attention should be paid, by specialized doctors in pediatric and adolescent gynecology, in DUB cases after menarche, while proper follow up of these girls is mandatory, due to their increased risk to manifest PCOS in the near future.

Chlamydia trachomatis infection and Vγ9Vδ2 Τ cells in women with recurrent spontaneous abortions.

PROBLEM: Vγ9Vδ2 T cells (γ9δ2) are involved in antibacterial immune responses. The aim of this study was to look for associations between peripheral blood (PB) γ9δ2 T cells and cervix/vaginal Chlamydia trachomatis (Ct) infection in women with recurrent spontaneous abortions (RSA). METHOD OF STUDY: Peripheral blood samples were obtained from 201 RSA women within 10 days after they experienced a new miscarriage. γ9δ2 T cells and their percentage in total γδ T cells were compared between women who had been found and women who had not been found infected with Ct (last 6 months). Fertile women (82) served as control subjects. RESULTS: The difference of mean percentages of γ9δ2 T cells between the abortion and control groups, and the Chlamydia (+) and Chlamydia (-) groups was highly statistically significant (P<.00001). Significant difference was also found between the Chlamydia (+) and Chlamydia (-) group and the control group (ANOVA). CONCLUSION: The measurement of γ9δ2T cells may be useful to suspect possibly undiagnosed chlamydial infection in RSA women.

Focus on BMI and subclinical hypothyroidism in adolescent girls first examined for amenorrhea or oligomenorrhea. The emerging role of polycystic ovary syndrome.

BACKGROUND: Primary amenorrhea, oligomenorrhea and secondary amenorrhea are diagnosed commonly during adolescence. Weight aberrations are associated with menstrual disorders. Autoimmune thyroiditis is frequent during adolescence. In this study, the commonest clinical and hormonal characteristics of amenorrhea or oligomenorrhea during adolescence were investigated. METHODS: In this cross-sectional study, one hundred and thirty-eight consecutive young patients presenting with amenorrhea or oligomenorrhea referred to an adolescent endocrinology and gynecology university clinic were studied. Clinical examination and an abdominal ultrasound were performed. Testosterone, free-testosterone, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, sex hormone binding globulin (SHBG), Δ4-androstenedione (Δ4A), free androgen index (FAI), insulin, glucose, thyroid stimulating hormone (TSH), total thyroxine (T4) (TT4), free T4 (FT4), total triiodothyronine (T3) (TT3) and free T3 (FT3). Concentrations were measured in blood samples. RESULTS: Patients with primary and secondary amenorrhea presented more often with body mass index (BMI) <18.5 and BMI >25 kg/m2, respectively. BMI values correlated positively with insulin (r=0.742) and glucose (r=0.552) concentrations and negatively with glucose/insulin ratio values (r=-0.54); BMI values and insulin concentrations correlated positively with FAI values (r=0.629 and r=0.399, respectively). In all patients, BMI values correlated positively and negatively with free testosterone (r=0.249) and SHBG (r=-0.24) concentrations, respectively. In patients with secondary amenorrhea insulin concentrations correlated negatively with SHBG concentrations (r=-0.75). In patients with oligomenorrhea BMI values correlated positively with insulin (r=0.490) and TSH (r=0.325) concentrations, and negatively with SHBG (r=-0.33) concentrations. Seventy-two percent, 21% and 7% of patients presented with TSH concentrations <2.5 µIU/mL, between 2.5 µIU/mL, 4.5 µIU/mL and >4.5 µIU/mL (subclinical hypothyroidism), respectively. Following the definition of polycystic ovary syndrome (PCOS) according to either the National Institutes of Health (NIH) criteria or those proposed in the literature by Carmina and his team, patients presented mainly with oligomenorrhea or secondary amenorrhea. There was good agreement between patients with amenorrhea or oligomenorrhea fulfilling both of the PCOS definition criteria employed. CONCLUSIONS: Among adolescent patients presenting with amenorrhea or oligomenorrhea for the first time those with low and high BMI present more often with primary and secondary amenorrhea, respectively. Obesity is involved in the development of hyperandrogenemia and hyperinsulinemia, particularly in PCOS patients. In these patients, subclinical hypothyroidism may be concealed and it should be investigated. These patients should be treated for abnormally increased or decreased BMI and be investigated for autoimmune thyroiditis.

Pregnancy outcome after oocyte donation in patients with Turner's syndrome: Clinical experience and management.

Turner's syndrome (TS) is a chromosomal defect with partial or total absence of the X chromosome. Our objective is to report our experience in Greece with patients suffering from TS and trying to conceive; therefore, we present four patients with TS, who underwent In vitro fertilization (ICSI) with donor oocytes in order to get pregnant. Three out of four patients managed to conceive and bring pregnancy to completion. It was shown that patients diagnosed in childhood or adolescence with TS have the possibility to undergo hormone replacement therapy (HRT) and thus, secondary sexual characteristics as well as uterus of almost normal size can develop. Assisted reproduction techniques (ART), predominantly with donated oocytes, could give these patients the possibility to have children.

Uterine cancer in the writings of ancient Greek physicians.

In this article, we present the views on uterine cancer of the ancient Greek physicians. We emphasize on uterine's cancer aetiology according to the dominant in antiquity humoural theory, on its surgical treatment suggested by Soranus of Ephesus, and in the vivid description provided by Aretaeus of Cappadocia. During that period, uterine cancer was considered as an incurable and painful malignancy and its approach was mainly palliative.

Uterine cancer in the writings of Byzantine physicians.

Byzantine physicians recognized uterine cancer as a distinct disease and tried to suggest a therapeutic approach. The work of Oribasius, Aetius of Amida, Paul of Aegina, Cleopatra Metrodora and Theophanes Nonnus reflects the Hippocratic-Galenic scientific ideas as well as their own concept on this malignancy. According to their writings uterine cancer was considered an incurable disease and its treatment was based mainly on palliative herbal drugs.