Structural analysis of the female reptile reproductive system by micro-computed tomography and optical coherence tomography†.

Volumetric data provide unprecedented structural insight to the reproductive tract and add vital anatomical context to the relationships between organs. The morphology of the female reproductive tract in non-avian reptiles varies between species, corresponding to a broad range of reproductive modes and providing valuable insight to comparative investigations of reproductive anatomy. However, reproductive studies in reptilian models, such as the brown anole studied here, have historically relied on histological methods to understand the anatomy. While these methods are highly effective for characterizing the cell types present in each organ, histological methods lose the 3D relationships between images and leave the architecture of the organ system poorly understood. We present the first comprehensive volumetric analyses of the female brown anole reproductive tract using two non-invasive, non-destructive imaging modalities: micro-computed tomography (microCT) and optical coherence tomography (OCT). Both are specialized imaging technologies that facilitate high-throughput imaging and preserve three-dimensional information. This study represents the first time that microCT has been used to study all reproductive organs in this species and the very first time that OCT has been applied to this species. We show how the non-destructive volumetric imaging provided by each modality reveals anatomical context including orientation and relationships between reproductive organs of the anole lizard. In addition to broad patterns of morphology, both imaging modalities provide the high resolution necessary to capture details and key anatomical features of each organ. We demonstrate that classic histological features can be appreciated within whole-organ architecture in volumetric imaging using microCT and OCT, providing the complementary information necessary to understand the relationships between tissues and organs in the reproductive system. This side-by-side imaging analysis using microCT and OCT allows us to evaluate the specific advantages and limitations of these two methods for the female reptile reproductive system.

Imaging approaches for the diagnosis of genetic diseases affecting the female reproductive organs and beyond.

This review aims to provide an overview of neoplastic lesions associated with genetic diseases affecting the female reproductive organs. It seeks to enhance our understanding of the radiological aspects in diagnosing genetic diseases including hereditary breast and ovarian cancer syndromes, Lynch syndrome, Peutz-Jeghers syndrome, nevoid basal cell carcinoma syndrome, and Swyer syndrome, and explores the patterns and mechanisms of inheritance that require elucidation. Additionally, we discuss the imaging characteristics of lesions occurring in other regions due to the same genetic diseases.

Longer anogenital distance in female fetus of diabetic and obese pregnant women.

OBJECTIVE: Previous studies revealed that prenatal exposure to androgen excess such as polycystic ovary syndrome (PCOS) is associated with offspring's anogenital distance (AGD) length, and AGD is a biomarker of intrauterine androgen exposure. This study aims to investigate a possible relationship of fetal AGD with maternal diabetes and obesity, and to evaluate whether AGD predicts the fetal androgen exposure related to diabetes and obesity in female fetus. This study is the first to focus on the relationship between offspring's AGD and maternal diabetes and obesity. MATERIALS AND METHODS: This is a prospective study investigating 218 pregnant women (125 in control group and 93 in study group). Fetal AGD was measured from the center of anus to the posterior convergence of the fourchette by ultrasound. Multivariate linear regression analysis was applied to assess the association of the fetal AGD length with maternal diabetes and obesity. RESULTS: The control patients had significantly shorter fetal AGD (mean:10.7 mm, P < 0.001) compared to diabetic, obese and diabetic obese patients (mean: 12.6 mm, 12.8 mm and 12.9 mm, respectively). The results of regression analysis showed that both maternal diabetes and obesity were significantly correlated with longer AGD in female fetus. The results confirmed also that offspring's AGD measurement in utero by ultrasound is feasible and reliable. CONCLUSION: The study findings suggest that both maternal diabetes and obesity are associated with intrauterine androgenic milieu during pregnancy, and fetal AGD may be used as a biomarker to predict this effect. This may provide important advantages in terms of early detection of reproductive system abnormalities related to prenatal androgen exposure.

MicroCT analysis unveils the role of inflatable female genitalia and male tibial complex in the genital coupling in the spider genus Aysha (Anyphaenidae, Araneae).

Sperm transfer in spiders is achieved by copulatory organs on the male pedipalps (i.e., copulatory bulbs), which can be simple or a complex set of sclerites and membranes. During copulation, these sclerites can be used to anchor in corresponding structures in the female genitalia by means of hydraulic pressure. In the most diverse group of Entelegynae spiders, the retrolateral tibial apophysis clade, the female role in the coupling of genitalia is considered rather passive, as conformational changes of the female genital plate (i.e., the epigyne) during copulation are scarce. Here, we reconstruct the genital mechanics of two closely related species belonging to the Aysha prospera group (Anyphaenidae) that bear a membranous, wrinkled epigyne and male pedipalps with complex tibial structures. By using microcomputed tomography data of a cryofixed mating pair, we reveal that most of the epigyne remains greatly inflated during genital coupling, and that the male tibial structures are coupled to the epigyne by the inflation of a tibial hematodocha. We propose that a turgent female vulva is a prerequisite for the genital coupling, which could implicate a female control device, and that the structures from the male copulatory bulb have been functionally replaced by tibial structures in these species. Furthermore, we show that the conspicuous median apophysis is maintained in spite of being functionally redundant, posing a puzzling situation.

The Development of Normal Fetal External Genitalia Throughout Gestation.

In this review, we describe normal development of fetal genitalia throughout gestation as well as the identification of normal male and female genitalia on ultrasound. We use abnormal and ambiguous genitalia as illustrative tools to assist with the identification of normal genitalia and recognition of some of the most common abnormalities in external genitalia development.

High-definition ultrasonography in the evaluation of the reproductive tract of bitches during the follicular phase of the estrous cycle.

The aim was to sonographically evaluate the reproductive tract of bitches during the follicular phase of the estrous cycle using High Density (HD) ultrasonic techniques. Females (n = 8) were evaluated at five different times throughout the follicular phase, as determined by vaginal cytology and blood progesterone concentrations. Ultrasonic exams were performed using the ACUSON S2000/SIEMENS device utilizing a multifrequency HD transducer (5.5-18 MHz). Videos of the ovaries were obtained and recordings were evaluated using a DICOM viewer software for counting and measuring the ovarian structures, which were assigned to groups based on diameter in mm: G1: ≤ 1; G2: from 1.01 to 3.5; G3 from 3.51 to 5.5; G4: from 5.51 to 10. There was a greater uterine thickness with the progression of the follicular phase (P < 0.05). Six distinct regions were identified in the uterine wall. The ovarian dimensions increased (P < 0.05) as stage of the follicular phase advanced. There was fluid detected around the ovaries after ovulation. There was a characteristic fat tissue hyperechogenicity around the ovaries at all timepoints. There was a difference in the number of ovarian structures of each dimension group at each time there were assessments (P < 0.05). There was a difference in diameter of the largest ovarian structure and in average value of wall thickness at all timepoints when there were evaluations (P < 0.05). The HD ultrasonography technique provides for excellent image resolution, allowing for a more precise characterization of the bitch's reproductive structures and changes occurring during the follicular phase of the estrous cycle.

The role of imaging in pelvic exenteration for gynecological cancers.

Pelvic exenteration (PE) is one of the most challenging gynecologic oncologic surgeries and is an overriding term for different procedures that entail radical en bloc resection of the female reproductive organs and removal of additional adjacent affected pelvic organs (bladder, rectum, anus, etc.) with concomitant surgical reconstruction to restore bodily functions. Multimodality cross-sectional imaging with MRI, PET/CT, and CT plays an integral part in treatment decision-making, not only for the appropriate patient selection but also for surveillance after surgery. The purpose of this review is to provide a brief background on pelvic exenteration in gynecologic cancers and to familiarize the reader with the critical radiological aspects in the evaluation of patients for this complex procedure. The focus of this review will be on how imaging can aid in treatment planning and guide management.

Incidentalomas of the female genital tract on 64-slice MDCT: a clinico-radiological pictorial review.

Sonography is the imaging modality of choice for diagnosing diseases of the female genital tract due to its high resolution, easy availability, low cost and lack of radiation. CT is not advocated for the primary evaluation of the female pelvis. However, with the advent of Multidetector CT (MDCT), females of all ages undergo CT scan of the abdomen and pelvis for myriad non-gynaecological diseases, e.g. subacute intestinal obstruction, abdominal lump, abdominal tuberculosis, appendicitis, ureteric colic, pancreatitis, oncological staging, follow-up, etc. Incidental female genital tract disorders were seen on these scans that are a dilemma for both, the radiologists and the clinicians. The objective of this pictorial review is to characterise the incidentally detected lesions of the female genital tract observed on 64-slice MDCT by correlating with sonography, if necessary, and establishing a clinico-radiological diagnosis. Our aim is to emphasise that the radiologist may be the first person to recognise a gynaecologic disorder and hence can play a significant role in patient management.

Radiomics in radiation oncology for gynecological malignancies: a review of literature.

Radiomics is the extraction of a significant number of quantitative imaging features with the aim of detecting information in correlation with useful clinical outcomes. Features are extracted, after delineation of an area of interest, from a single or a combined set of imaging modalities (including X-ray, US, CT, PET/CT and MRI). Given the high dimensionality, the analytical process requires the use of artificial intelligence algorithms. Firstly developed for diagnostic performance in radiology, it has now been translated to radiation oncology mainly to predict tumor response and patient outcome but other applications have been developed such as dose painting, prediction of side-effects, and quality assurance. In gynecological cancers, most studies have focused on outcomes of cervical cancers after chemoradiation. This review highlights the role of this new tool for the radiation oncologists with particular focus on female GU oncology.

Effects of experimental exposure to zearalenone on reproductive system morphometry, plasma oestrogen levels, and oocyte quality of beef heifer.

The aim of the present study was to evaluate the effects of zearalenone (ZEA) on the reproductive system morphometry, oestrogen (E2) levels and oocyte quality of beef heifers. Twenty non-pregnant purebred Nellore (Bos indicus) heifers [age, ≥18 months; initial body weight, 348 ± 30 kg (mean ± standard deviation)] were used. The animals were randomly divided into experimental group and a control group of 10 animals each. Group experimental was administered 300 ppb ZEA per os for 98 days, and the control group was administered placebo per os for 98 days. The administration of ZEA was carried out daily by adding mycotoxin to the diet. All heifers were evaluated weekly via rectal ultrasound examinations (12 weeks). Diameters of the right and left uterine horns, right and left ovaries, largest antral follicle and corpus luteum were measured. Vulva size was also measured. Blood samples were collected to estimate E2 levels. At the end of 12 weeks, the heifers were slaughtered, and the ovaries were sent to the laboratory for in vitro embryo production. A completely randomized design was adopted, and repeated measures analysis of variance (p < .05) was performed (except for oocyte quality). Vulva size (p = .0985); diameters of uterine horns (p = .0522), ovaries (p = .6955), antral follicles (p = .6355) and corpus luteum (p = .3808); and E2 levels (p = .3379) were not affected by the treatments. ZEA-contaminated diet significantly reduced (p = .05) the proportion of viable oocytes (49.4%, n = 207) compared with the control diet (59.9%, n = 222); however, the blastocyst rate did not differ between the groups (p = .9418). The results indicate that contamination of beef heifer's diet with 300 ppb ZEA affected neither morphometric parameters nor plasma oestrogen levels; however, ZEA contamination was detrimental to oocyte quality.

Prepubescent Female Genital Examination Images: Evidence-Informed Learning Opportunities.

OBJECTIVES: To determine diagnoses and image features that are associated with difficult prepubescent female genital image interpretations. DESIGN AND SETTING: This was a mixed-methods study conducted at a tertiary care pediatric center using images from a previously developed education platform. PARTICIPANTS: Participants comprised 107 medical students, residents, fellows, and attendings who interpreted 158 cases to derive case difficulty estimates. INTERVENTIONS: This was a planned secondary analysis of participant performance data obtained from a prospective multi-center cross-sectional study. An expert panel also performed a descriptive review of images with the highest frequency of diagnostic error. MAIN OUTCOME MEASURES: We derived the proportion of participants who interpreted an image correctly, and features that were common in images with the most frequent diagnostic errors. RESULTS: We obtained 16,906 image interpretations. The mean proportion correct scores for each diagnosis were as follows: normal/normal variants 0.84 (95% confidence interval [CI] 0.82, 0.87); infectious/dermatology pathology 0.59 (95% CI 0.45, 0.73); anatomic pathology 0.61 (95% CI 0.41, 0.81); and, traumatic pathology 0.64 (95% CI 0.49, 0.79). The mean proportion correct scores varied by diagnosis (P < .001). The descriptive review demonstrated that poor image quality, infant genitalia, normal variant anatomy, external material (eg, diaper cream) in the genital area, and nonspecific erythema were common features in images with lower accuracy scores. CONCLUSIONS: A quantitative and qualitative examination of prepubescent female genital examination image interpretations provided insight into diagnostic challenges for this complex examination. These data can be used to inform the design of teaching interventions to improve skill in this area.

Systematization for female genital anatomic variations.

INTRODUCTION: Congenital variations of the reproductive system arise during embryonal organogenesis, although their clinical manifestations present later in adolescence or during reproductive years due to functional disorders such as abnormal menstruation, sexual dysfunction, infertility, and pregnancy loss. Surgical treatment of congenital variations is performed according to variant anatomy and functional disorders. However, many congenital anatomic variations are difficult to categorize based on current classification systems. The aim of this study is to distinguish female genital anatomic variations for appropriate surgical treatment based on a clinical analysis of uterovaginal malformations and disorders of sex development. The deviant anatomy defined as variations, which has been used in the manuscript instead of anomalies. MATERIALS AND METHODS: A retrospective review was conducted of 718 cases of uterovaginal malformation and 144 cases with disorders of sex development. Physical variations were assessed by ultrasound, magnetic resonance imaging, and laparoscopy. Genetic studies were conducted for individuals with disorders of sex development. Classification of variants was determined by physical findings, genetic findings, and clinical presentations. RESULTS: A unified systematization for female genital anatomic variations was proposed, based on the genome (karyotype), gonadal morphology, internal and external genital anatomy. The internal anatomy was classified to uterovaginal variations, which have distinguished to 11 basic types and 24 variants, according to morphologic patterns. Surgical treatments are proposed based on these variants. CONCLUSION: These new classifications provide a framework for clinical management and appropriate surgical treatment of female genital anatomic variants, with the aim of improving reproductive outcomes.

3D in situ imaging of the female reproductive tract reveals molecular signatures of fertilizing spermatozoa in mice.

Out of millions of ejaculated sperm, a few reach the fertilization site in mammals. Flagellar Ca2+ signaling nanodomains, organized by multi-subunit CatSper calcium channel complexes, are pivotal for sperm migration in the female tract, implicating CatSper-dependent mechanisms in sperm selection. Here using biochemical and pharmacological studies, we demonstrate that CatSper1 is an O-linked glycosylated protein, undergoing capacitation-induced processing dependent on Ca2+ and phosphorylation cascades. CatSper1 processing correlates with protein tyrosine phosphorylation (pY) development in sperm cells capacitated in vitro and in vivo. Using 3D in situ molecular imaging and ANN-based automatic detection of sperm distributed along the cleared female tract, we demonstrate that spermatozoa past the utero-tubal junction possess the intact CatSper1 signals. Together, we reveal that fertilizing mouse spermatozoa in situ are characterized by intact CatSper channel, lack of pY, and reacted acrosomes. These findings provide molecular insight into sperm selection for successful fertilization in the female reproductive tract.

When mammals mate, males ejaculate millions of sperm cells into the females' reproductive tract. But as the sperm travel up the tract, only a handful of the 'fittest' sperm will actually manage to reach the egg. This process of elimination prevents the egg from being fertilized by multiple sperm cells and stops the eggs from being fertilized outside of the womb. A lot of what is known about fertilization in mammals has come from studying how sperm and eggs cells interact in a Petri dish. However, this approach cannot explain how sperm are selected and removed as they journey towards the egg. Previous work suggests that a calcium channel, which sits in the membrane surrounding the sperm tail, may provide some answers. The core of this channel, known as CatSper, is made up of four proteins arranged into a unique pattern similar to racing stripes. Without this specific arrangement, sperm cells cannot move forward and fertilize the egg in time. To investigate the role of this protein in more depth, Ded et al. established a new way to image the minute structures of sperm cells, such as CatSper, in the reproductive tract of female mice. Experiments in a Petri dish revealed that sperm cells that have been primed to fertilize the egg are a diverse population: in some cells one of the proteins that make up the calcium channel, known as CatSper1, is cleaved, while in other cells this protein remains intact. Visualizing this protein in the female reproductive tract showed that sperm cells close to the site of fertilization contain non-cleaved CatSper1. Whereas sperm cells further away from the egg ­ and thus closer to the uterus ­ are more likely to contain broken down CatSper1. Taken together, these findings suggest that the state of the CatSper1 protein may be used to select sperm that are most likely to reach and fertilize the egg. Future studies should address what happens to the calcium channel once the CatSper1 protein is cleaved, and how this channel controls the movements and lifespan of sperm. This could help identify new targets for contraception and improve current strategies for assisted reproduction.

Endometrial Cancer, the Current International Federation of Gynecology and Obstetrics Staging System, and the Role of Imaging.

Imaging plays a crucial role in the diagnosis, staging, and follow-up of endometrial cancer. Endometrial cancer is staged surgically using the International Federation of Gynecology and Obstetrics (FIGO) staging system. Preoperative imaging can complement surgical staging but is not yet considered a required component in the current FIGO staging system. Preoperative imaging can help identify some tumor characteristics and tumor spread, both locally and distally. More accurate assessment of endometrial cancers optimizes management and treatment plan, including degree of surgical intervention. In this article, we review the epidemiology, FIGO staging system, and the importance of imaging in the staging of endometrial cancer.

Are anogenital distance and external female genitalia development changed in neural tube defects? Study in human fetuses.

BACKGROUND: Anogenital distance (AGD), the distance from the anus to the genitals, is a marker of normal genital development. AGD and other biometric parameters of external female genitalia are important as ultrasonographic markers that can determine fetal gender in the first trimester. Neural tube defects are one of the commonest congenital malformations of the central nervous system, with anencephaly being the most severe defect. Female genitalia development and their association with anencephaly have not been previously described. AIM: The aim of this study was to compare the biometric parameters of external female genitalia in fetuses with anencephaly and compare it to the parameters of normocephalic fetuses at different gestational ages. STUDY DESIGN: We studied 34 female fetuses, 22 normocephalic and 12 anencephalic, aged between 12 and 22 weeks post-conception. The fetuses were placed in the classic lithotomy position and before the fetal dissection, the external female genitalia were photographed with a digital camera. Biometric parameters were recorded and measurements were performed using the Image J software, version 1.46r. Clitoral length and width, clitoris to anus distance, vaginal opening length and width, vaginal opening to labia majora distance, and AGD were measured (Figure). For statistical analysis, the Wilcoxon-Mann-Whitney test was used (p < 0.05). RESULTS: We observed a significant difference between some measurements of the groups: the vaginal opening width was significantly greater in anencephalic fetuses and the vaginal opening length, clitoris to anus distance and vaginal opening to labia majora distance were significantly greater in normocephalic fetuses. For the clitoris length and width, we did not find statistical differences. We also did not find statistical significance in AGD between groups (normocephalic 2.32 mm [2.46-6.42/SD = 2.17] vs. anencephalic 3.93 mm [1.15-6.65/SD = 1.93]; p = 0.499). The linear regression analysis indicated that AGD increased more with age in anencephalic than in the normocephalic group, but without significant differences (r2 = 0.01677; p < 0.318). DISCUSSION: This article is the first to report the female external genitalia parameters in fetuses with anencephaly. In our study we observed some alterations in biometry of the external genitalia in anencephalic fetuses, with a pattern of morphological reduction in this group. The vaginal opening length, clitoris to anus distance and vaginal opening to labia majora distance were significantly lower in anencephalic fetuses but we did not find statistical significance in clitoris measurements and AGD. CONCLUSIONS: Anencephalic fetuses had some alterations in external genitalia development, but the anogenital distances did vary significantly between the groups.

Simulation-based clinical learning for the third year medical student: Effectiveness of transabdominal and transvaginal ultrasound for elucidation of OB/GYN scenarios.

PURPOSE: Point-of-care ultrasound (POCUS) is gaining recognition as a teaching modality that acts as an integrative learning tool during medical student transition to clinical rotations. This study aimed to determine if the use of ultrasound simulation enhances understanding of Obstetrical and Gynecological (Ob/Gyn) anatomy and pathology in third-year medical students (M3), and if M3 students found the simulator useful. METHODS: M3 students taking the OB/Gyn clerkship were invited to participate. Baseline knowledge of pelvic ultrasound anatomy and pathology was assessed with a multiple-choice question test. Participants received a one-hour OB/Gyn ultrasound simulation training session. A post-test assessed knowledge after the intervention. Survey data was collected regarding learning styles and learner satisfaction. RESULTS: Following simulator-based training, the median correct number of responses to the knowledge questions increased from 11 of 18 to 14 of 18 correct (P < .001). Statistically significant increases were also observed in comfort level with OB/GYN ultrasound (P < .001). All 68 students answered that the ultrasound simulator was helpful and enjoyed using the simulator. CONCLUSIONS: This study suggests that ultrasound simulators are useful for improvement in knowledge, comfort level, and ability to identify pathology in Ob/Gyn scenarios in M3 students.

Sonoanatomy of female reproductive organ of Sunda porcupine (Hystrix javanica).

The conventional anatomical study of specimens requires cutting processes which destruct the limited specimens. A non-destructive method, namely an ultrasonography, can be used to assess the anatomical organ information of those specimens. The aim of this research is to analyse the macroanatomy of the female reproductive organ in the Sunda porcupine (Hystrix javanica), using ultrasonographical imaging. In this study, four formaldehyde-fixed reproductive organ specimens of the Sunda porcupine were used. A 10-12 MHz linear ultrasound transducer was utilized to provide an imaging format of both longitudinal and transversal views. Photographic images were then used as comparison with a sonographic image. The results show that the ultrasound image of the Sunda porcupine reproductive organ soft tissue was hypoechoic, the lumen and antrum follicles were anechoic, while atretic follicles and the mons pubis were hyperechoic. Generally, the size of the organ was not significantly different between photographical and ultrasonographical imaging (p > .05). In conclusion, ultrasound images can be utilized for anatomical studies of the Sunda porcupine reproductive organs without destructing the specimen.

Menstrual Pattern, Reproductive Hormones, and Transabdominal 3D Ultrasound in 317 Adolescent Girls.

CONTEXT: The knowledge of normal variation of reproductive hormones, internal genitalia imaging, and the prevalence of gynecological disorders in adolescent girls is limited. OBJECTIVE: The study aimed to describe reproductive parameters in postmenarchal girls from the general population including the frequency of oligomenorrhea, polycystic ovary syndrome, and use of hormonal contraception. DESIGN: The Copenhagen Mother-Child Cohort is a population-based longitudinal birth cohort of 1210 girls born between 1997 and 2002. SETTING: University hospital. PARTICIPANTS: A total of 317 girls were included, with a median age of 16.1 years and time since menarche of 2.9 years. MAIN OUTCOME MEASURE(S): Tanner stage, height, weight, age at menarche, menstrual cycle length and regularity, ovarian/uterine volume, and number of follicles were recorded. Serum concentrations of FSH, LH, anti-Müllerian hormone (AMH), inhibin B, estradiol, testosterone, SHBG, androstenedione, dehydroepiandrosterone sulfate, 17-OH-progesterone, and IGF-1 were measured. RESULTS: Twenty girls (6.3%) had oligomenorrhea and differed significantly in serum androgens and AMH, age at and time since menarche from girls with regular cycles. Twenty-seven girls were classified with PCOS (8.5%) and had significantly higher 17-OH-progesterone, estradiol, AMH, LH, and age at menarche than the reference group. Girls on oral contraception had significantly higher serum SHBG concentrations and lower serum concentrations of all hormones except AMH and IGF-1. Ovarian follicles 2 to 29.9 mm correlated positively with serum AMH (P < 0.0001). CONCLUSIONS: Most 16-year-old girls had regular menstrual cycles, normal reproductive hormones, and uterine and ovarian ultrasound. Serum AMH reflected ovarian follicle count and may be a useful biomarker of ovarian reserve.