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.

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.

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.

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.

Primary amenorrhea in adolescent girls: normal coitus or not? Always take a look in the physician's office.

BACKGROUND: Primary care physicians are frequently faced with the challenge of evaluating primary amenorrhea in adolescent girls. Approximately 15% of these women have abnormal genital examination, with Müllerian agenesis being the second most frequent cause. We report two cases of adolescents with Müllerian agenesis that presented to a tertiary adolescent medicine center with primary amenorrhea and the very rare sexual phenomenon of urethral coitus. The aim of this report is to emphasize the importance of performing a genital examination in girls who present with amenorrhea in the primary care setting, even if 'normal' vaginal sexual activity is assumed. CASE PRESENTATIONS: A 19-year-old Caucasian and a 16-year-old Filipino girl presented to a tertiary adolescent medicine center with primary amenorrhea and a history of 'normal' vaginal coitus. Investigation revealed Müllerian agenesis in association with urethral coitus in both cases; neither patient suffered significant urethral damage to require urethra reconstruction. However, the first adolescent had recurrent pyelonephritis and renal scarring and the second had dysuria.To the best of our knowledge, Case 1 also represents the second reported case of pituitary prolactinoma in association with Müllerian agenesis. The first adolescent underwent a hernia repair and vaginoplasty, whereas the second had vaginal dilatations. CONCLUSION: Our cases highlight the need for careful assessment of the external genitalia and vagina patency in all girls with amenorrhea, even if they report 'normal' vaginal sexual activity. Early identification of anatomic disorders such as Müllerian agenesis, will allow provision of proper care according to the patient's needs and the existing abnormalities, and prevention of rare, unintentional but potentially physically and emotionally harmful, patterns of sexual intercourse.

The effect of hormone therapy on biochemical and ultrasound parameters associated with atherosclerosis in 46,XY DSD individuals with female phenotype.

The aim of this study was to evaluate the effect of hormone therapy (HT) in the endothelial function of 46,XY disorders of sexual development (DSD) patients with female phenotype. Biochemical and ultrasound measurements were performed in 20 patients at initiation of oral 2 mg 17ß-estradiol/1 mg norethisterone acetate, and after 6 months of therapy. Lipid profile, including total cholesterol (TC), LDL, HDL, triglycerides (TG) and Atherogenic Index of Plasma (AIP), as well as levels of VE-Cadherin, E-Selectin, Thrombomodulin and vWf were determined. Ultrasonographic examinations included evaluation of flow-mediated dilatation (FMD) and measurement of Carotid and Femoral Intima Media Thickness (IMT). HT raised HDL (35.4 mg/dl versus 40.1 mg/dl, p = 0.019) while lowering TG (166 mg/dl versus 109 mg/dl, p = 0.026) and AIP (0.24 versus 0.04, p = 0.007). No changes were noted in TC and LDL (215.7 mg/dl versus 192.25 mg/dl and 87.46 mg/dl versus 76.35 mg/dl, respectively). There was significant reduction of VE-Cadherin (4.05 ng/ml versus 2.20 ng/ml, p = 0.002) and E-selectin (73.98 ng/ml versus 56.73 ng/ml, p = 0.004). No change was observed in Thrombomodulin and vWf (11.76 ng/ml versus 13.90 ng/ml and 80.75% versus 79.55%, respectively). FMD improved significantly (5.4% versus 8.15%, p = 0.003), while only carotid bulb IMT decreased significantly (0.65 mm versus 0.60 mm, p = 0.018). Overall, HT was found to improve biochemical and ultrasound markers of endothelial function in 46,XY DSD patients with female phenotype.

ENhancinG vAGinal dElivery in Greece through educational and behavioral interventions among maternity care providers regarding labor management: the ENGAGE stepped-wedge randomized prospective trial protocol.

BACKGROUND: There is an emerging need to systematically investigate the causes for the increased cesarean section rates in Greece and undertake interventions so as to substantially reduce its rates. To this end, the ability of the participating Greek obstetricians to follow evidence-based guidelines and respond to other educational and behavioral interventions while managing labor will be explored, along with barriers and enablers. Herein discussed is the protocol of a stepped-wedge designed intervention trial in Greek maternity units with the aforementioned goals in mind, named ENGAGE (ENhancinG vAGinal dElivery in Greece). METHODS: Twenty-two selected maternity units in Greece will participate in a multicenter stepped-wedge randomized prospective trial involving 20,000 to 25,000 births, with two of them entering the intervention period of the study each month (stepped randomization). The maternity care units entering the study will apply the suggested interventions for a period of 8-18 months depending on the time they enter the intervention stage of the study. There will also be an initial phase of the study lasting from 8 to 18 months including observation and recording of the routine practice (cesarean section, vaginal birth, and maternal and perinatal morbidity and mortality) in the participating units. The second phase, the intervention period, will include such interventions as the application of the HSOG (the Hellenic Society of Obstetrics and Gynecology) Guidelines on labor management, training on the correct interpretation of cardiotocography, and dealing with emergencies in vaginal deliveries, while the steering committee members will be available to discuss and implement organizational and behavioral changes, answer questions, clarify relevant issues, and provide practical instructions to the participating healthcare professionals during regular visits or video conferences. Furthermore, during the study, the results will be available for the participating units in order for them to monitor their own performance while also receiving feedback regarding their rates. Τhe final 2-month phase of the study will be devoted to completing follow-up questionnaires with data concerning maternal and neonatal morbidities that occurred after the completion of the intervention period. The total duration of the study is estimated at 28 months. The primary outcome assessed will be the cesarean section rate change and the secondary outcomes will be maternal and neonatal morbidity and mortality. DISCUSSION: The study is expected to yield new information on the effects, advantages, possibilities, and challenges of consistent clinical engagement and implementation of behavioral, educational, and organizational interventions described in detail in the protocol on cesarean section practice in Greece. The results may lead to new insights into means of improving the quality of maternal and neonatal care, particularly since this represents a shared effort to reduce the high cesarean section rates in Greece and, moreover, points the way to their reduction in other countries. TRIAL REGISTRATION: NCT04504500 (ClinicalTrials.gov). The trial was prospectively registered. Ethics Reference No: 320/23.6.2020, Bioethics and Conduct Committee, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

PON1-108 TT and PON1-192 RR genotypes are more frequently encountered in Greek PCOS than non-PCOS women, and are associated with hyperandrogenaemia.

OBJECTIVE: To investigate the frequencies of three paraoxonase (PON)1 polymorphisms in Greek polycystic ovary syndrome (PCOS) and non-PCOS women, and their genotypes association with hyperandrogenaemia and insulin resistance. DESIGN: Case-control genetic association study. SETTING: University Hospital Endocrine Unit. PATIENTS: A total of 142 PCOS cases (NIH criteria) and 112 controls. MAIN OUTCOME MEASURE: Genotyping of the c.-108C>T (PON1-108), the c.163T>A (PON1-55) and the c.575A>G (PON1-192) polymorphisms and measurement of baseline androgen and insulin resistance profile. RESULTS: The PON1-108 TT and PON1-192 RR genotypes were more frequently encountered in the PCOS than in the control group. The PON1-192 R allele frequency was greater in the PCOS than in the control group. Comparing the PCOS and the control groups, statistical significances favoured a recessive and a dominant genetic model, respectively, for the single PON1-108 T and PON1-192 R alleles. Free Androgen Index (FAI) levels were higher in patients with PON1-108 TT, whereas Testosterone, FAI and Dehydroepiandrosterone sulphate (DHEAS) levels were higher in patients with PON1-192 RR than patients with the wild or the heterozygous genotype. CONCLUSIONS: The decreased PON1 activity-associated PON1-108 TT and the PON1-192 RR genotypes are more frequently found in Greek PCOS women and are associated with hyperandrogenaemia. Hyperandrogenaemia must depend also on other genetic factors because the same genotypes were not associated with hyperandrogenaemia in the control group. Through identification of the involved polymorphisms, women with PCOS could potentially have a better therapeutic screening.

Interleukin-15 (IL-15) and anti-C1q antibodies as serum biomarkers for ectopic pregnancy and missed abortion.

Given the present lack of clinically useful tests for the accurate diagnosis of ectopic pregnancy (EP), there is a need to select out those immunological factors measured in the maternal serum, as potential biomarkers. Our assumption was that C1q/anti-C1q antibody complexes and serum levels of interleukin-15 (IL-15) may play a role in differentiating abortions (MAs) and EPs and normal pregnancies. We assessed whether their measurement could set the diagnosis in a case control study at 6-8 weeks consisting of 60 women with failed early pregnancy (30 EPs, 30 MAs) and 33 women with intrauterine pregnancies. Normal pregnancies contain anti-C1q antibodies more frequently compared to women with failed pregnancies, the lowest levels being found in EPs, but this lacked statistical significance and anti-C1q could not serve as a marker. However EP pregnancies had elevated IL-15 levels that could statistically significantly differentiate them from MAs and IUPs. Furthermore, when assessing IL-15 for the clinically important differentiation between IUP and EP, we found at a cut-off of 16 pg/mL a negative predictive value of 99 with a sensitivity for diagnosing an EP of 92%. According to these results, serum IL-15 is a promising marker differentiating an MA from an EP.

Abnormal uterine bleeding and dysfunctional uterine bleeding in pediatric and adolescent gynecology.

Abnormal uterine bleeding (AUB), which is defined as excessively heavy, prolonged and/or frequent bleeding of uterine origin, is a frequent cause of visits to the Emergency Department and/or health care provider. While there are many etiologies of AUB, the one most likely among otherwise healthy adolescents is dysfunctional uterine bleeding (DUB), which is characterizing any AUB when all possible underlying pathologic causes have been previously excluded. The most common cause of DUB in adolescence is anovulation, which is very frequent in the first 2-3 post-menarchal years and is associated with immaturity of the hypothalamic - pituitary - ovarian axis. Management of AUB is based on the underlying etiology and the severity of the bleeding and primary goals are prevention of complications, such as anemia and reestablishment of regular cyclical bleeding, while the management of DUB can in part be directed by the amount of flow, the degree of associated anemia, as well as patient and family comfort with different treatment modalities. Treatment options for DUB are: combined oral contraceptives (COCs), progestogens, non steroidal anti inflammatory drugs (NSAIDs), tranexamic acid (anti-fibrinolytic), GnRH analogues, Danazol and Levonorgestrel releasing intra uterine system (LNG IUS).

HPV infection: immunological aspects and their utility in future therapy.

High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, and alterations in the microenvironment of the lesion. Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans cells fail to present the antigens efficiently, tumor-associated macrophages aggregate resulting in an unsuccessful immune response by the host. HPV products also downregulate the expression of microenvironment components which are necessary for natural-killer cells response and antigen presentation to cytotoxic cells. Additionally HPV promotes T-helper cell 2 (Th2) and T-regulatory cell phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity and lesion progression to cancer. Humoral response after natural infection is inefficient, and neutralizing antibodies are not adequate in many women. Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to stimulate cellular immune response against the virus and alter the milieu of the lesion.

Response to hormonal treatment of young females with primary or very premature ovarian failure.

The aim of this study was to evaluate the impact of hormone treatment (HT) on several endocrinologic, metabolic and bone parameters in young women with primary or very premature ovarian failure. The study included 40 phenotypically females of 14-20 years old with primary or secondary amenorrhoea and female external genitalia. Study subjects were categorised in three groups: Group A included 12 subjects with Turner syndrome, Group B included 19 subjects with Swyer syndrome and Group C included 9 subjects with very premature ovarian failure. HT was administered for 24 months and included conjugated oestrogens and medroxyprogesterone acetate. In all groups, HT provided a beneficial hormonal profile and resulted in safe and adequate serum oestrogens levels. In Group A, no adverse effects on metabolic or coagulation parameters were noted; significant increases in high-density lipoprotein cholesterol (HDL) levels and bone density were observed. Similar positive effects of HT were observed in Group B. Finally, in Group C, no adverse effects of HT were noted, but the favourable increase in HDL was absent; bone density kept significantly increasing until the 12-month evaluation. In conclusion, the administration of HT is remarkably beneficial for young women with primary or very premature ovarian failure.

Maternal serum resistin concentrations in gestational diabetes mellitus and normal pregnancies.

AIM: To investigate changes in maternal serum resistin levels during pregnancy and postpartum and clarify their relationship to insulin resistance. METHODS: Thirty normal pregnant women were compared to 30 women diagnosed with gestational diabetes mellitus (GDM). Serum resistin levels were collected at the time of glucose challenge test (26-28 weeks), at 38 gestational weeks and at the third postpartum day and measured with enzyme immunoassay. Correlation of resistin to the homeostatic model assessment-insulin resistance (HOMA-IR) was performed. RESULTS: Maternal serum resistin levels at 38 weeks were significantly higher in pregnant women with GDM compared to the control group (0.28 vs 0.21 ng/mL, P = 0.02) and the same was true for the immediate puerperium (0.25 vs 0.19 ng/mL, P = 0.03). A significant increase in resistin levels was observed in GDM women from 26-28 weeks to 38 weeks (0.21 vs 0.28 ng/mL, P = 0.02), but not in controls. A decrease in serum resistin levels was noted in both the GDM and control groups, at 38 weeks and the immediate postpartum period, but this decrease did not reach statistical significance in either of the two groups. Resistin levels were positively correlated to HOMA-IR at 26-28 weeks of gestation (r = +0.253, P = 0.05). CONCLUSION: GDM is associated with increased resistin serum levels in term pregnancy as well as postpartum. Resistin is positively correlated to HOMA-IR at 26-28 weeks of gestation. A reduction in maternal resistin after delivery indicates a significant placental or fetal contribution in the production of resistin.

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.

A unique case of trichorionic quadruplet pregnancy after oocyte donation in a patient with Turner's syndrome.

A 26-year old patient with a mosaic (45X/46XX) Turner's syndrome and secondary amenorrhea since the age of 19, was referred to the IVF unit for participation in oocyte donation program. After a complete work up including meticulous cardiological assessment, she had endometrial preparation with a high dose hormonal regimen, and transfer of three embryos derived from donated oocytes. An ongoing trichorionic quadruplet pregnancy was confirmed on ultrasound. The couple was offered fetal reduction to twins at 12 gestational weeks after consultation stressing the risks of a quadruplet pregnancy in general and especially in a patient with Turner's syndrome. No pregnancy or maternal complications were encountered and the patient delivered two healthy babies by lower segment cesarean section after spontaneous rupture of membranes at 36 gestational weeks.