Kisspeptin对女性生殖功能调控机制的研究进展

在女性生殖活动中,kisspeptin参与调控下丘脑-垂体-性腺(HPG)轴的功能,并通过介导雌激素的正负反馈调节促性腺激素释放激素(Gn RH)的分泌,解除促性腺激素抑制激素(Gn IH)对HPG轴的负性调控作用,继而调节促性腺激素(Gn)的分泌及类固醇甾体激素的分泌,并与多种卵巢功能异常疾病的病理过程密切相关。Kisspeptin可调控卵泡发育和排卵发生,并影响子宫内膜容受性的形成。此外,在辅助生殖技术(ART)过程中kisspeptin可代替传统h CG扳机,并降低接受ART治疗的不孕症女性卵巢过度刺激综合征(OHSS)的发生。     

外源性促性腺激素治疗低促性腺激素性闭经不孕症患者的疗效观察

目的观察外源性促性腺激素治疗低促性腺激素性闭经不孕症患者的疗效。方法选取我院2014年6月~2015年4月收治的低促性腺激素性闭经不孕症患者68例作为研究对象,所有患者均采用外源性促性腺激素治疗,观察并对比治疗前后子宫相关指标、生殖激素水平变化情况及妊娠成功率。结果治疗后,所有患者子宫相关指标水平与生殖激素各水平均比治疗前高,差异有统计学意义(P0.05)。结论低促性腺激素性闭经不孕症患者行外源性促性腺激素治疗,可有效改善子宫变化与生殖激素水平,值得临床推广与应用。     

外源性促性腺激素治疗低促性腺激素性闭经不孕症患者的疗效

目的 探讨在低促性腺激素性闭经不孕症患者治疗中,采用外源性促性腺激素治疗方案的疗效。方法 选取低促性腺激素性闭经不孕症患者32例作为研究对象,给予其外源性促性腺激素治疗,治疗期间随时注意观察患者卵泡变化,并在适当时机指导患者同房,观察妊娠效果、生殖激素水平及子宫变化。结果治疗后生殖激素水平各项指标均有非常显著的提升,差异有统计学意义(P0.05);治疗后患者子宫各项指标均有非常显著的提升;妊娠成功率为96.88%。结论 通过外源性促性腺激素治疗低促性腺激素性闭经不孕症,可有效改善生殖激素水平和子宫变化,帮助其成功妊娠。     

低促性腺激素性腺功能减退症的促排卵治疗——附2例临床分析

目的:探讨低促性腺激素性腺功能减退症的促排卵治疗方案。方法:使用hMG联合人绒毛膜促性腺激素(hCG)对2例低促性腺激素性腺功能减退症患者进行促排卵治疗,应用阴道超声和血清FSH、性激素测定监测卵泡发育。在卵泡发育成熟后给予hCG诱发排卵。结果:2例患者共进行4个周期的促排卵治疗,在给予hMG后卵泡发育缓慢或无卵泡发育时,添加hCG100~200 IU,均成功诱发排卵,并获得2例临床妊娠。结论:hMG和低剂量hCG联合使用能有效进行低促性腺激素性腺功能减退症患者的促排卵治疗。     

男子和妇女低促性腺激素性疾病:诊断和脉冲式促性腺激素释放素治疗

低促性腺激素性性功能减退(HH)是一种可发生于两性的临床综合征。其外周血中促性腺激素(Gn)正常或略低,而性腺却无功能,长期以来使临床医师迷惑不解。本文用多次取样测定Gn水平的方法做为衡量下丘脑促性腺激素释放素(GnRH)分泌的指标,验证了以下假说:本病代表了多种形式的内源性GnRH脉冲式释放异常。在对正常男女进行广泛研究并建立正常值后,发现HH男女患者中,有GnRH分泌量的异常,包括GnRH分泌完全缺如、分泌的幅度和频率有缺陷,以及释放的Gn生物活性异常。此外,采用符合生理的外源性GnRH替代治疗方案以模拟内源性GnRH分泌的正常频率,可使低Gn性男女患者生殖和生育功能完全恢复正常。因此,本病的异型性及其对GnRH满意的临床和生化反应提示其基本缺陷是下丘脑部分或完全性合成和/或释放GnRH障碍。维持内源性GnRH分泌的生理频率和幅度对正常生殖功能是必不可少的。     

以46, XY完全型性腺发育不全为表现的Frasier综合征1例

本文分析Frasier综合征在性发育异常患者中的临床表现及致病基因特征, 具体为回顾性分析1例46, XY Frasier综合征患者的生殖系统发育和解剖特点、性激素情况、基因检测结果及性腺的手术病理结果。本例患者在性发育方面表现为"46, XY完全型性腺发育不全", 病因系WT1基因9号内含子c.1432+5G>A的剪接突变, 已被报道为Frasier综合征的致病突变。生殖激素符合高促性腺素低性激素血症;术中所见符合幼女盆腔, 未发现肾Wilms瘤;性腺病理一侧为发育不良的卵巢, 另一侧为性腺母细胞瘤。其肾病起病年龄为7岁, 活检病理符合局灶节段性肾小球硬化症, 激素原发抵抗, 已进展为终末期肾病。Frasier综合征可表现为慢性进展性肾病、46, XY性发育异常及性腺肿瘤三联征, 与WT1基因9号内含子剪接突变有关;若为46, XY性腺发育不全, 尤其是Frasier综合征患者, 性腺肿瘤发生率高、恶变率高, 应积极切除双侧附件, 并依据肾病状态, 及时开始性激素补充治疗。     

促性腺激素释放激素在女性生殖系统的分布与作用

促性腺激素释放激素(gonadotropin releasing hormone,GnRH)是下丘脑分泌的十肽激素,对生殖调控具有重要意义。人体中存在2种亚型,即GnRH-I和GnRH-II,以及2种相应的受体GnRHR-I和GnRHR-II。GnRH除了通过垂体性腺轴控制女性的发育、生殖功能外,同时还以自分泌和旁分泌的方式作用于垂体外组织,如乳腺、胎盘、卵巢、子宫内膜等。GnRH或许可作为乳腺癌的一种有效治疗和预防恶化的方法。GnRH类似物已经用于治疗许多激素相关的疾病,尤其是与子宫相关的疾病,如子宫内膜增生、子宫内膜癌、子宫内膜异位症(EMs),可降低子宫颈癌的风险等。胎盘自身可生成GnRH或GnRH样多肽物质,离体的胎盘组织体外培养表明,GnRH可显著增加胎盘组织人绒毛膜促性腺激素(hCG)的释放。局部的GnRHs对维持卵巢功能具有重要的作用;卵巢GnRHs参与正常和异常生殖组织的内分泌调控。     

促性腺激素释放激素及其受体研究进展

促性腺激素释放激素（GnRH）是由下丘脑分泌的神经内分泌因子。其通过下丘脑-垂体-性腺轴调节女性发育和生殖功能,同时还以自分泌和旁分泌的方式作用于垂体外组织。研究发现,GnRH及其受体均存在多种亚型,并在正常及异常生殖相关组织,包括子宫内膜异位症、子宫内膜癌和卵巢癌等表达。了解GnRH不同亚型的作用机制进而开发其类似物,以达到治疗子宫内膜异位症、不孕和肿瘤等妇科疾病的目的,是国外最新研究的热点之一。     

促性腺激素释放激素及其受体研究进展

促性腺激素释放激素（GnRH）是由下丘脑分泌的神经内分泌因子。其通过下丘脑-垂体-性腺轴调节女性发育和生殖功能,同时还以自分泌和旁分泌的方式作用于垂体外组织。研究发现,GnRH及其受体均存在多种亚型,并在正常及异常生殖相关组织,包括子宫内膜异位症、子宫内膜癌和卵巢癌等表达。了解GnRH不同亚型的作用机制进而开发其类似物,以达到治疗子宫内膜异位症、不孕和肿瘤等妇科疾病的目的,是国外最新研究的热点之一。     

静脉内注射促性腺激素释放激素后血葡萄糖水平急骤升高对黄体生成素和促卵泡激素释放的影响

早期的研究已经证实妇女生殖周期的正常神经内分泌控制取决于下丘脑促性腺激素释放激素(GnRH)的分泌和垂体前叶的促性腺激素(黄体生成素LH和促卵泡激素FSH)释放的反应。现代强调生殖周期中断的原因常常合并有疾病状态。糖尿病是常见生殖周期异常的一种疾患。本文观察了血葡萄糖急骤升高对垂体腺释放促性腺激素(LH和FSH)的影响。21名妇女接受两次静脉内注射100微克的GnRH,在这两次注射     

Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis

The objective of the study is to summarize the clinical characteristics of 33 patients’ cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients’ information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53?±?3.60 years old, 165?±?6.49?cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41?±?21.50 mIU/mL) and LH (27.10?±?8.47 mIU/mL) and low level of E2 (8.85?±?6.13?pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38?±?0.60)?×?(1.38?±?0.70)?×?(1.38?±?0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required.     

Management of phenotypic female patients with an XY karyotype

Nine phenotypic female patients with XY karyotype were evaluated through a clinical, cytogenetic, hormonal, endoscopic and histologic diagnostic protocol. Seven patients complained of primary amenorrhea and two patients of abnormal puberal development. The final diagnosis was XY gonadal dysgenesis (n = 5) and testicular feminization syndrome (n = 4). Two patients were less than 155 cm tall, and the remainder were over 155. Minor somatic anomalies were found in two patients with XY gonadal dysgenesis. Patient with testicular feminization syndrome had FSH and LH within the normal range, and patients with XY gonadal dysgenesis had elevated FSH and LH levels. Gonadoblastomas were found in two patients with XY gonadal dysgenesis (one patient with XO/XX/XY mosaicism). Laparoscopy and gonadal biopsy might be useful in some patients to avoid confusion between XY gonadal dysgenesis and testicular feminization syndrome. Early diagnosis of XY gonadal dysgenesis is always desirable, and bilateral gonadectomy is indicated as soon as the diagnosis is made in patients with a Y chromosome and elevated FSH levels. Surgical removal of the gonads from patients with testicular feminization should be delayed until the completion of puberty because of the low risk of malignancy.     

Gonadendysgenesie

In gonadal dysgenesis, differentiation of the primitive gonad to mature gonads is missing. The main symptoms include primary amenorrhea and missing secondary sexual development. To the gynecologist, pure gonadal dysgenesis 46,XX and 46,XY, mixed gonadal dysgenesis, and Turner’s syndrome are clinically important. In all patients with gonadal dysgenesis containing Y chromosome material (e.g. Swyer’s syndrome), removal of the gonads is highly recommended in order to prevent malignancy. The risk of malignancy in these organs is about 25%. Estrogen and progestogen replacement therapy is advocated at the onset of puberty for the induction of female sexual characteristics and prevention of the sequelae of chronic estrogen deficiency. Turner’s syndrome shows typical additional symptoms requiring an interdisciplinary approach, including pediatricians and internists.     

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome.     

The pure gonadal dysgenesis syndrome.

Two cases of gonadal dysgenesis in phenotypic females associated with different chromosomal patterns are discussed. Both patients presented with primary amenorrhea and were characterized by tall stature and underdeveloped secondary sex characteristics and external and internal reproductive organs. The karyotype of the first patient was 46,XX with a satellite on chromosome 17. The second patient had a normal female chromosome composition (46,XX) with a past history of mumps. Laparoscopic bilateral gonadal biopsies in both patients revealed fibrous tissue without any primordial follicles. This report emphasizes the pathogenesis, clinical significance, diagnosis and management of gonadal dysgenesis.     

Familial Swyer syndrome: a rare genetic entity

Swyer syndrome is a pure gonadal dysgenesis associated with a 46 XY karyotype and primary amenorrhea in a phenotypic female. Individuals in this syndrome are at an increased risk for development of gonadal malignancies. Swyer syndrome (gonadal dysgenesis) running in families is rare event and few such scenarios were reported in the literature. Here we are presenting this rare entity involving three affected siblings born to a non-consanguineous couple. Index case - A 23-year-old female with primary amenorrhea is presented with a mass per abdomen. The clinical findings and laboratory investigations revealed hypergonadotropic hypogonadism picture and, imaging revealed a left ovarian tumor. Primary surgical debulking of ovarian cancer was done, histopathology of which revealed a dysgerminoma FIGO stage IIIC. The family history of the patient revealed a similar pattern as the elder sister had primary amenorrhea and had succumbed to ovarian cancer and the younger sister also has primary amenorrhea. Karyotype of all the three patients revealed a male genotype with a female phenotype. The early diagnosis of the patients with Swyer syndrome is very important because of the increased risk for the development of malignancy. This is a rare event to have two sisters with ovarian cancers in three siblings affected with familial gonadal dysgenesis syndrome each of them having a different genotype and first of its kind to ever be reported in literature.     

Chromosomal complements in primary gonadal failure

Twenty-nine patients underwent clinical, hormonal, endoscopic, and cytogenetic studies to determine the cause of primary amenorrhea or delayed sexual development. In 19 of them (mean age 17.6 years), the X chromosome was either missing or anomalous. In ten patients (mean age 25.5 years), the chromosomal complement was normal, 46 XX in six patients and 46 XY in four patients. Those with abnormal chromosomal complements were shorter (mean height, 141.9 cm) than patients with normal complements (158.7 cm). Somatic stigmas were observed more frequently in patients with chromosomally abnormal primary gonadal failure. In 23 patients (79.3%), the gonads were streaks, with fibrous stroma devoid of either follicles or tubules containing germ cells. In three patients the ovaries were hypoplastic, with few primordial follicles. Gonadoblastoma was present in two patients with XY and mixed XX/X/XY gonadal dysgenesis. In every patient with streak gonads and lack of germ cells, serum gonadotropin levels were elevated. Karyotype, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) assays, and eventually laparoscopy and gonadal biopsy are important in the management of patients with primary gonadal failure.     

Treatment of congenital anomalies in girls and women

The presence of a Y chromosome in patients with gonadal dysgenesis requires removal of the streak gonads for fear of tumor formation, the most likely one a gonadoblastoma. When estrogen-progestin replacement is given to patients with gonadal dysgenesis, sampling of the endometrium at regular intervals should be done in order to screen for endometrial hyperplasia. Obstructive lesions of the müllerian ducts should be diagnosed promptly to allow egress of the menstrual flow and preserve reproductive function. It is advisable to delay construction of an artificial vagina for patients with congenital absence of the vagina until such time as the patient is interested in sexual activity and motivated sufficiently to use a vaginal form on a regular basis postoperatively. Genetic females with ambiguous external genitalia should be evaluated carefully to make sure that they do not have the salt-losing variety of the adrenogenital syndrome, which can be life threatening.     

Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis

BackgroundDisorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation.CaseWe present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor.Summary and ConclusionTo our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.     

Malignant Stromal Tumour of the Ovary with Virilizing Effects in an XXX Female with Streak Ovaries

Summary: In gonadal dysgenesis, the presence of the Y sex chromosome appears to have a strong influence on the development of germ cell tumours. The risk of malignancy associated with other sex chromosomal abnormalities is much lower. In the present report, the clinical manifestations – including primary amenorrhoea, tall stature, infertility and poor development of the genitalia and breasts – associated with a predominantly 47, XXX karyotype are described. Malignant change of the streak ovary to an unusual gonadal stromal tumour with lipid-containing cells occurred at a late stage in her life, and this was associated with progressive virilization and production of androgenic and oestrogenic steroids. In view of the risk of malignancy as well as the abnormal endocrine effects, especially in the presence of a Y chromosome, there is a place for the prophylactic removal of these dysgenetic gonads.