RESUMO
PURPOSE: As a further step to elucidate the actual diverse spectrum of oncofertility practices for breast cancer around the globe, we present and discuss the comparisons of oncofertility practices for breast cancer in limited versus optimum resource settings based on data collected in the Repro-Can-OPEN Study Part I & II. METHODS: We surveyed 39 oncofertility centers including 14 in limited resource settings from Africa, Asia & Latin America (Repro-Can-OPEN Study Part I), and 25 in optimum resource settings from the United States, Europe, Australia and Japan (Repro-Can-OPEN Study Part II). Survey questions covered the availability of fertility preservation and restoration options offered to young female patients with breast cancer as well as the degree of utilization. RESULTS: In the Repro-Can-OPEN Study Part I & II, responses for breast cancer and calculated oncofertility scores showed the following characteristics: (1) higher oncofertility scores in optimum resource settings than in limited resource settings especially for established options, (2) frequent utilization of egg freezing, embryo freezing, ovarian tissue freezing, GnRH analogs, and fractionation of chemo- and radiotherapy, (3) promising utilization of oocyte in vitro maturation (IVM), (4) rare utilization of neoadjuvant cytoprotective pharmacotherapy, artificial ovary, and stem cells reproductive technology as they are still in preclinical or early clinical research settings, (5) recognition that technical and ethical concerns should be considered when offering advanced and innovative oncofertility options. CONCLUSIONS: We presented a plausible oncofertility best practice model to guide oncofertility teams in optimizing care for breast cancer patients in various resource settings.
Assuntos
Neoplasias da Mama , Preservação da Fertilidade , Neoplasias , Neoplasias da Mama/complicações , Embrião de Mamíferos , Feminino , Humanos , Técnicas de Maturação in Vitro de Oócitos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: The epidermal growth factor (EGF) signaling system regulates trophoblast differentiation, and its disruption could contribute to perinatal disease. We hypothesized that this pathway is altered in preeclampsia, a disorder associated with trophoblast apoptosis and failure to invade and remodel the uterine spiral arteries. METHODS: Six EGF family peptides and a truncated EGF receptor splice variant (p110/EGFR) were examined using immunohistochemistry in the trophoblast of placentas (N = 76) from women with preeclampsia, and compared to placentas from women of similar gestational age (GA) with preterm labor (PTL) or small for gestational age (SGA) fetuses, as well as normal term placentas. EGF, transforming growth factor-α (TGFA), and heparin-binding EGF-like growth factor (HBEGF) were evaluated using ELISA in maternal plasma from another 20 pregnancies with or without preeclampsia. Cell death was evaluated in the HTR-8/SVneo human cytotrophoblast cell line using TUNEL to evaluate the protective effects of EGF peptides. RESULTS: Trophoblast HBEGF, TGFA, and EGF were significantly reduced in preeclampsia compared to PTL and SGA, while p110/EGFR accumulated significantly on the surface of the chorionic villi (p < 0.05). Plasma EGF levels were significantly decreased in preeclamptic patients, compared to non-preeclamptic patients (p < 0.05). HBEGF, EGF, TGFA, epiregulin, and betacellulin each blocked cytotrophoblast cell death in vitro (p < 0.05). DISCUSSION: Three members of the EGF family are dysregulated in placentas with preeclampsia, whereas p110/EGFR, a potential EGF receptor antagonist, is overexpressed. These findings are consistent with the concept that disruption of the EGF signaling system contributes to aberrant trophoblast development associated with preeclampsia.
Assuntos
Regulação para Baixo , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/antagonistas & inibidores , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Adulto , Apoptose , Linhagem Celular Transformada , Vilosidades Coriônicas/metabolismo , Vilosidades Coriônicas/patologia , Estudos de Coortes , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/química , Receptores ErbB/química , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/sangue , Humanos , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Placenta/patologia , Placentação , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/patologia , Gravidez , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fator de Crescimento Transformador alfa/sangue , Trofoblastos/metabolismo , Trofoblastos/patologia , Adulto JovemRESUMO
The objectives of this study were to determine whether antiprogestin therapy or the infusion of human CG to mimic blastocyst transit in the baboon alters heparin-binding EGF-like growth factor expression during the window of implantation. During the menstrual cycle, heparin-binding EGF-like growth factor protein accumulation in the glandular epithelium was low in the proliferative phase and increased to maximal expression on d 5 and 10 postovulation. Stromal cells accumulated high levels of heparin-binding EGF-like growth factor in the proliferative phase, which decreased by d 5 postovulation. These transitional changes in both cell types were delayed when cycling baboons were treated with the antiprogestin ZK 137.316 during the luteal phase. The treatment with human CG had no effect on expression of heparin-binding EGF-like growth factor when compared with cycling baboons on d 10 postovulation and was comparable with that observed on d 18 and 22 of pregnancy. However, the superimposition of the antiprogestin with the human CG treatment also decreased expression in the epithelial cells. In summary, heparin-binding EGF-like growth factor accumulation in the epithelial glands is under the influence of progesterone and does not seem to be influenced by the paracrine secretion of trophoblast CG.
Assuntos
Gonadotropina Coriônica/farmacologia , Fator de Crescimento Epidérmico/biossíntese , Papio/fisiologia , Progestinas/antagonistas & inibidores , Animais , Blastocisto/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Feminino , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Imuno-Histoquímica , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular , Comunicação Parácrina/efeitos dos fármacos , Comunicação Parácrina/fisiologia , Gravidez , Progesterona/farmacologia , Sondas RNA/farmacologia , Esteroides/farmacologia , Células Estromais/efeitos dos fármacosRESUMO
Embryonic expression of the epidermal growth factor (EGF) receptor as well as embryonic and steroid-dependent uterine secretion of its ligand, heparin-binding EGF-like growth factor (HB-EGF), are temporally associated with the period of blastocyst implantation. We examined the temporal cell type-specific expression of HB-EGF in human endometrium during the menstrual cycle by immunohistochemistry and in situ hybridization. Early first trimester implantation sites were also examined to determine HB-EGF protein levels in decidual and fetal tissues. In the endometrial stroma, HB-EGF protein expression increased markedly during the late proliferative phase and then decreased in the early secretory phase. By contrast, luminal and glandular epithelial cells as well as blood vessel endothelium accumulated the protein between midcycle and cycle day 20, with peak expression observed during the period of uterine receptivity for implantation. HB-EGF expression decreased dramatically at the end of the cycle, before menses. Spatiotemporal expression of HB-EGF messenger ribonucleic acid demonstrated a similar pattern. During early pregnancy, HB-EGF immunostaining was noted in the decidua and in both villous and extravillous trophoblast populations. These findings suggest that HB-EGF promotes implantation and trophoblast invasion through paracrine and autocrine signaling as cells penetrate the stroma and displace the arteriole endothelium.
Assuntos
Endométrio/fisiologia , Fator de Crescimento Epidérmico/fisiologia , Ciclo Menstrual , Placentação/fisiologia , Adolescente , Adulto , Decídua/metabolismo , Implantação do Embrião , Endométrio/química , Endotélio Vascular/metabolismo , Fator de Crescimento Epidérmico/análise , Fator de Crescimento Epidérmico/genética , Células Epiteliais/metabolismo , Feminino , Feto/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Imuno-Histoquímica , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular , Gravidez , RNA Mensageiro/análise , Células Estromais/metabolismoRESUMO
OBJECTIVE: To incorporate conservative management of a heterotopic pregnancy using injection of KCl into the ectopic pregnancy (EP). DESIGN: A retrospective case report. SETTING: A patient referred to an academic institution in the division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, incorporating the ultrasound (US) and operating room facilities. INTERVENTION(S): Using US as a guide, KCl was injected into the chorionic cavity of an EP. MAIN OUTCOME MEASURE(S): Resolution of ectopic gestational tissue with resultant hematosalpinx requiring exploratory laparotomy. Uncomplicated prenatal course of intrauterine pregnancy. RESULT(S): Injection of KCl into the chorionic cavity of EP resulting in resolution of gestational tissue but complicated by hematosalpinx in the fallopian tube. CONCLUSION(S): Selective embryo reduction of a tubal heterotopic pregnancy remains a viable therapeutic option.
Assuntos
Doenças das Tubas Uterinas/induzido quimicamente , Hemorragia/induzido quimicamente , Cloreto de Potássio/efeitos adversos , Redução de Gravidez Multifetal , Gravidez Ectópica/terapia , Feminino , Humanos , Injeções , Cloreto de Potássio/uso terapêutico , GravidezRESUMO
OBJECTIVES: To determine if Poloxamer 407 (poloxamer, Pluronic F-127; BASF Wyandotte Corp., Parsippany, NJ) is as effective as Interceed(TC7) (Ethicon, a Johnson and Johnson company, Sommerville, NJ) in preventing postoperative adhesion formation using the rat uterine horn model and to determine if the presence of blood or lactated Ringer's solution affects the effectiveness of Poloxamer 407. DESIGN, SETTING, PARTICIPANTS: Sprague-Dawley white rats, weighing 225 to 250 g in a conventional laboratory setting. The left or right sidewall was randomly assigned to receive no treatment (control), Interceed(TC7), or poloxamer. INTERVENTIONS: Each uterine horn and ipsilateral sidewall was subjected to a standardized lesion of denudation. To evaluate the barrier agents in the presence of blood, a sidewall vessel was ligated and a thrombus allowed to form. To evaluate the effectiveness of lactated Ringer's solution, 10 mL was injected intraperitoneally after abdominal closure. MAIN OUTCOME MEASURES: Degree of adhesion formation was evaluated 14 days after surgery. RESULTS: The adhesion score for the poloxamer-treated animals was significantly lower than its control. Interceed(TC7) did not reduce adhesion formation as compared with its control. In animals that received both poloxamer and Interceed(TC7) on either side, the poloxamer-treated sides had a significantly lower adhesion score than Interceed(TC7)-treated sides. The presence of blood and lactated Ringer's reduced the adhesion-reducing properties of poloxamer. CONCLUSION: In this model, poloxamer is more effective than Interceed(TC7) in the prevention of postoperative adhesion formation. These findings also suggest that the presence of blood compromises the effectiveness of poloxamer to prevent postoperative adhesion formation, therefore requiring complete hemostasis before poloxamer's application. Lactated Ringer's instillation was ineffective in reducing adhesion formation on the control or poloxamer-treated sidewall.
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Celulose Oxidada/uso terapêutico , Poloxaleno/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Útero/cirurgia , Animais , Feminino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To assess the efficacy of a bioabsorbable gel for reducing primary postoperative adhesions. DESIGN: A randomized, prospective, blinded study. SETTING: Academic research environment. ANIMALS: Forty-one New Zealand Rabbits. INTERVENTION(S): A chemically modified hyaluronate and carboxymethylcellulose (HA/CMC) gel formulation was applied to a bilateral uterine horn injury. Postoperative adhesions were assessed at a second-look laparoscopy. MAIN OUTCOME MEASURE(S): The uterine horn model was shown to be adhesiogenic, with 29 (70%) of 42 untreated uterine horns found to have adhesions. After gel treatment, 22 (55%) of 40 uterine horns were free of adhesions compared with 12 (30%) of 42 controls. RESULT(S): Animals treated with HA/CMC gel had significantly reduced postsurgical adhesion scores when compared with controls. CONCLUSION(S): Treatment of injured uterine horn with HA/CMC gel resulted in a significant reduction in postoperative surgical adhesions.
Assuntos
Carboximetilcelulose Sódica , Géis , Ácido Hialurônico , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Doenças Uterinas/prevenção & controle , Animais , Feminino , Coelhos , Útero/cirurgiaRESUMO
OBJECTIVE: To evaluate the luteal phase in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months duration, with no male factor, anatomic-functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); [3] ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles, normal hormonal screen, and were matched for age and BMI to patients. MAIN OUTCOME MEASURE(S): Pattern of follicular growth rate and luteal phase hormonal profile. RESULT(S): Women with unexplained infertility did not differ in menstrual cycle characteristics, follicular growth rate or mean preovulatory follicle diameter, or endometrial biopsy dating. The mean levels of P tended to be lower in the unexplained infertility group throughout the luteal phase, but only the midluteal interval reached statistical significance. Luteal phase mean integrated P or urinary PDG levels of unexplained infertility women did not differ from those of fertile controls. The ratio of integrated E2:P also was significantly greater in women with unexplained infertility than in fertile controls. CONCLUSION(S): Women with rigorously defined unexplained infertility have subtle hormonal anomalies during the luteal phase when compared with fertile controls.
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Infertilidade Feminina/etiologia , Ciclo Menstrual , Adulto , Biópsia , Índice de Massa Corporal , Temperatura Corporal , Endométrio/patologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Feminina/classificação , Infertilidade Feminina/fisiopatologia , Fase Luteal , Hormônio Luteinizante/sangue , Masculino , Folículo Ovariano/diagnóstico por imagem , Ovulação , Progesterona/sangue , Valores de Referência , UltrassonografiaRESUMO
No detrimental effect on sperm motility characteristics by PF from women with low-stage endometriosis was documented when incubated for 3 to 6 hours. Although 1 of 31 women with endometriosis possessed IgA and IgG to sperm in her PF, its significance remains undetermined.
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Anticorpos/análise , Endometriose/imunologia , Motilidade dos Espermatozoides , Espermatozoides/imunologia , Líquidos Corporais/imunologia , Feminino , Humanos , Masculino , Cavidade Peritoneal , Valores de Referência , SucçãoRESUMO
OBJECTIVE: To determine hormone levels across the menstrual cycle in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the following rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months' duration, with no male factor, anatomic or functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); (3) ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles and normal hormonal screens, and were matched for age and BMI with patients. MAIN OUTCOME MEASURE(S): Daily gonadotropin and steroid hormone levels across the menstrual cycle. RESULT(S): Basal FSH and LH levels in the early, middle and late follicular phases were increased significantly in the group with unexplained fertility compared with the normal controls. The mean (+/-SD) early follicular FSH levels were 7.0 +/- 0.57 mIU/mL in the unexplained-infertility group and 4.7 +/- 0.37 mIU/mL (conversion factor to SI units, 1.00) in the normal controls, respectively. There was no difference between groups over the periovulatory or luteal phase. Midluteal mean (+/-SD) P levels were lower in the unexplained-infertility group than in the normal controls (13.7 +/- 1.6 versus 24.0 +/- 3.2 ng/mL [conversion factor to SI units, 3.180]). Mean E2 concentrations were elevated in the group with unexplained infertility versus normal controls in the early through the late follicular phase but reached significance only in the midfollicular phase. Mean prolactin levels were elevated consistently across the menstrual cycle in the unexplained-infertility group compared with those in normal controls but reached significance only in the early and late follicular and midluteal phases of the cycle. Cortisol concentrations were similar between the two groups. CONCLUSION(S): These data indicate that there are subtle alterations in various hormones measured across the menstrual cycle in women with unexplained infertility compared with those in normal controls, suggesting a diminished ovarian reserve.