Joseph S. Sanfilippo

Adolescent endometriosis: diagnosis and treatment approaches.

OBJECTIVES To review the etiologies, diagnosis, and treatment options of adolescent endometriosis. METHODS Review of publications relating to adolescent endometriosis. RESULTS Endometriosis occurs in adolescents as young as 8 years of age; furthermore, there have been documented cases of endometriosis occurring prior to menarche. Adolescents presenting with pelvic pain are treated with cyclic combination oral contraceptive pills and nonsteroidal anti-inflammatory agents. If the pain does not respond to these therapies, then in adolescents as in adults, an operative laparoscopy is recommended for the diagnosis and surgical management of endometriosis. The operating gynecologist should be familiar with the appearance of the complete spectrum of various morphologies of endometriosis, as adolescents tend to have clear, red, white, and/or yellow-brown lesions more frequently than black or blue lesions. Subtle clear lesions of endometriosis may be better visualized by filling the pelvis with irrigation fluid so that the clear lesions can be appreciated in a three-dimensional appearance. Young women who are found to have endometriosis by laparoscopy may present with acyclic, cyclic, and constant pelvic pain. Adolescents with pelvic pain not responding to conventional medical therapy have approximately a 70% prevalence of endometriosis. It is known that endometriosis is a progressive disease and since there is no cure, adolescents with endometriosis require long-term medical management until the time in their lives when they have completed childbearing. Psychosocial support is extremely important for this population of young women with endometriosis. CONCLUSIONS Endometriosis occurs in adolescents, and presenting symptoms may vary from those seen in adult women with the disease. All health care providers must be aware of the existence of adolescent endometriosis. They should also be aware of the presenting symptoms so that the adolescent can be appropriately referred to a gynecologist comfortable with medical and surgical treatment options in this patient population. If laparoscopy is to be undertaken, the gynecologist must be prepared not only to diagnose but to surgically manage endometriosis. In addition, the subtle laparoscopic findings of endometriosis in adolescents must be recognized for an appropriate diagnosis. Long-term medical therapy will hopefully decrease pain and the progression of the disease, thus decreasing the risk of advanced-stage disease and infertility.

X-Linked TEX11 Mutations, Meiotic Arrest, and Azoospermia in Infertile Men

BACKGROUND The genetic basis of nonobstructive azoospermia is unknown in the majority of infertile men. METHODS We performed array comparative genomic hybridization testing in blood samples obtained from 15 patients with azoospermia, and we performed mutation screening by means of direct Sanger sequencing of the testis-expressed 11 gene (TEX11) open reading frame in blood and semen samples obtained from 289 patients with azoospermia and 384 controls. RESULTS We identified a 99-kb hemizygous loss on chromosome Xq13.2 that involved three TEX11 exons. This loss, which was identical in 2 patients with azoospermia, predicts a deletion of 79 amino acids within the meiosis-specific sporulation domain SPO22. Our subsequent mutation screening showed five novel TEX11 mutations: three splicing mutations and two missense mutations. These mutations, which occurred in 7 of 289 men with azoospermia (2.4%), were absent in 384 controls with normal sperm concentrations (P=0.003). Notably, five of those TEX11 mutations were detected in 33 patients (15%) with azoospermia who received a diagnosis of azoospermia with meiotic arrest. Meiotic arrest in these patients resembled the phenotype of Tex11-deficient male mice. Immunohistochemical analysis showed specific cytoplasmic TEX11 expression in late spermatocytes, as well as in round and elongated spermatids, in normal human testes. In contrast, testes of patients who had azoospermia with TEX11 mutations had meiotic arrest and lacked TEX11 expression. CONCLUSIONS In our study, hemizygous TEX11 mutations were a common cause of meiotic arrest and azoospermia in infertile men. (Funded by the National Institutes of Health and others.).

Eliminating malignant contamination from therapeutic human spermatogonial stem cells.

Spermatogonial stem cell (SSC) transplantation has been shown to restore fertility in several species and may have application for treating some cases of male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich SSCs from human testis cell suspensions and also remove malignant contamination. We used flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT-4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not expressed on human spermatogonia. A multiparameter sort of MOLT-4-contaminated human testicular cell suspensions was performed to isolate EpCAM+/HLA-ABC-/CD49e- (putative spermatogonia) and EpCAM-/HLA-ABC+/CD49e+ (putative MOLT-4) cell fractions. The EpCAM+/HLA-ABC-/CD49e- fraction was enriched for spermatogonial colonizing activity and did not form tumors following human-to-nude mouse xenotransplantation. The EpCAM-/HLA-ABC+/CD49e+ fraction produced tumors following xenotransplantation. This approach could be generalized with slight modification to also remove contaminating TF-1a leukemia cells. Thus, FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression.

Pediatric and Adolescent Gynecologic Laparoscopy

Minimally invasive techniques to treat children and adolescents requiring surgery have increasingly become standard of care. Similarly, gynecologists frequently use laparoscopy to treat pelvic pathology. We present the necessary equipment and surgical techniques required to perform gynecologic procedures on the pediatric and adolescent population. We will give particular focus to the treatment of adnexal masses, chronic pelvic pain, endometriosis, and ovarian torsion. We will also discuss the role of the incidental appendectomy in children and adolescents.

Paracrine and epigenetic control of trophectoderm differentiation from human embryonic stem cells: the role of bone morphogenic protein 4 and histone deacetylases.

Our understanding of paracrine and epigenetic control of trophectoderm (TE) differentiation is limited by available models of preimplantation human development. Simple, defined media for selective TE differentiation of human embryonic stem cells (hESCs) were developed, enabling mechanistic studies of early placental development. Paracrine requirements of preimplantation human development were evaluated with hESCs by measuring lineage-specific transcription factor expression levels in single cells and morphological transformation in response to selected paracrine and epigenetic modulators. Bone morphogenic protein 4 (BMP4) addition to feeder-free pluripotent stem cells on matrigel frequently formed CDX2-positive TE. However, BMP4 or activin A inhibition alone also produced a mix of mesoderm and extraembryonic endoderm under these conditions. Further, BMP4 failed to form TE from adherent hESC maintained in standard feeder-dependent monolayers. Given that the efficiency and selectivity of BMP4-induced TE depended on medium components, we developed a basal medium containing insulin and heparin. In this medium, BMP4 induction of TE was dose dependent and with activin A inhibition by SB431542 (SB), approached 100% of cells. This paracrine stimulation of pluripotent cells transformed colony morphology from a cuboidal to squamous epithelium quantitatively on day 3, and produced significant multinucleated syncytiotrophoblasts by day 8. Addition of trichostatin A, a histone deacetylase (HDAC) inhibitor, reduced HDAC3, histone H3K9 methylation, and slowed differentiation in a dose-dependent manner. Modulators of BMP4- or HDAC-dependent signaling might adversely influence the timing and viability of early blastocyst developed in vitro. Since blastocyst development is synchronized to uterine receptivity, epigenetic regulators of TE differentiation might adversely affect implantation in vivo.

Endometriosis and the adolescent.

The majority of women with endometriosis report symptoms starting in adolescence, yet endometriosis is often a delayed diagnosis in this patient population. Given that endometriosis is felt to be a progressive disease with increasing morbidities over time, such as structural defects and infertility, being more aggressive with pursuing the diagnosis is warranted. Once the diagnosis of endometriosis is made, various medical and surgical treatment modalities are available, and this article will review the most current treatment recommendations.

Evaluation and Management of Dysmenorrhea in Adolescents

Chronic pelvic pain is defined by the American College of Obstetricians and Gynecologists (ACOG) as noncyclic pelvic pain of at least 3 months duration or cyclic pain of 6-month duration, either of which interferes with ones normal activities of daily living. Dysmenorrhea, or painful menses, is the most common gynecologic complaint among adolescent and young adult females and is the leading cause of recurrent short-term school or work absenteeism. This chapter reviews the assessment, diagnosis, and treatment of some of the most common causes of pelvic pain in adolescents.

Substance P in peritoneal fluid

Substance P is a neuropeptide that has been identified in the ovary, fallopian tube, uterus, and vagina and in the hypothalamic-pituitary axis in both an animal model and human ovaries. We sought to determine if substance P is present in peritoneal fluid and, if so, whether it correlated with the cause of infertility. Its presence was determined by radioimmunoassay in the peritoneal fluid of 66 patients undergoing diagnostic laparoscopy for clinical indications related to infertility. Total volume of peritoneal fluid and cycle day were recorded; patients were evaluated in groups according to diagnosis: endometriosis (n = 24), pelvic adhesions (n = 18), and normal controls (n = 24). The level of substance P (mean +/- SEM) was 122 +/- 19 pg/ml for endometriosis and 130 +/- 19 pg/ml for pelvic adhesions. These values were not significantly different from the normal controls (130 +/- 25 pg/ml). There was no significant difference in levels between follicular and luteal phase of the menstrual cycle. We conclude that substance P is present normally in peritoneal fluid and that its levels are not affected by pelvic endometriosis or adhesions.

Clinical pediatric and adolescent gynecology

Clinical pediatric and adolescent gynecology / , Clinical pediatric and adolescent gynecology / , کتابخانه دیجیتال جندی شاپور اهواز

Bleeding and vulvovaginitis in the pediatric age group.

Vaginal bleeding and vulvovaginitis are common clinical problems in the pediatric patient. Careful attention to historical and physical findings usually can resolve the problem at the initial visit. Knowledge of the differential diagnoses--including bacterial, nonspecific origins, dermatologic, traumatic, foreign bodies, neoplastic, urologic, precocious pubertal, or exogenous steroid ingestion--allows the clinician to include all significant causes of vaginal bleeding in this age group.