性腺发育异常患者的生育问题

性腺发育异常是指患者性腺性别异常的一类先天性疾病。现代诊疗多采用激素补充和手术治疗,可有效促进性腺发育异常患者内外生殖器的发育,维持激素平衡,并预防肿瘤发生。在对性腺发育异常患者进行管理的过程中,需对患者的生殖潜力予以考虑。尽管大部分性腺发育异常患者合并不孕,但辅助生殖技术为性腺发育异常患者提供了供卵、体外受精-胚胎移植等多种治疗选择。性腺发育异常患者可通过个体化的治疗成功妊娠并分娩正常胎儿,获得良好的母婴结局,实现生育愿望。文章着重就性腺发育异常患者的生殖潜力及生育问题的治疗进行阐述。     

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.     

Sex chromosomal mosaicism in the gonads of patients with gonadal dysgenesis, but normal female or male karyotypes in lymphocytes

OBJECTIVES: In most cases, XX or XY gonadal dysgenesis remains genetically unexplained. In this pilot study we searched for sex-chromosomal mosaicism in gonads of patients with XX or XY gonadal dysgenesis of undetermined origin. STUDY DESIGN: Gonadal tissues were analyzed by cytogenetic and interphase fluorescence in-situ hybridization (FISH) analyses in four patients with gonadal dysgenesis and normal female (46,XX) or male (46,XY) karyotypes in lymphocytes. RESULTS: Cytogenetic and FISH analyses of the gonads demonstrated in three patients a sex-chromosomal mosaicism. Cytogenetic analysis of gonadal tissue of the fourth patient confirmed the result of the lymphocytes with 46,XX, but FISH analysis revealed in 17% of nuclei only one X-chromosome. CONCLUSION: Our data indicate that sex-chromosomal mosaicism in gonads may be a frequent cause of gonadal dysgenesis despite of normal karyotypes in lymphocytes. Therefore, cytogenetic and FISH analyses of gonadal tissue can provide important information in unexplained cases of gonadal dysgenesis.     

Testicular feminization syndrome in the neonate

If we see a young, phenotypically female patient with an XY karyotype, it is of great importance to differentiate between the testicular feminization syndrome and gonadal dysgenesis. Patients with testicular feminization will always have normal testes, which are situated either in the ovarian fossa or in the inguinal canal. Patients with gonadal dysgenesis always have streak gonads. The risk of developing a malignancy in an abnormally located testis is very low, certainly before puberty, whereas the risk for dysgenetic gonads to develop a malignancy is high. Testes in patients with testicular feminization have an important endocrine function in puberty, whereas in gonadal dysgenesis patients they do not. For these reasons, in patients with testicular feminization, one should not remove the testes until the completion of puberty, whereas in patients with gonadal dysgenesis removal should be performed immediately upon recognition of the disorder.     

A Rare Case of Intersex: 46XY Gonadal Dysgenesis

EDITORIAL COMMENT: We accepted this case for publication not only because of its rare interest but because it will remind readers that patients with primary amenorrhoea require karyotyping and consideration of gonadal dysgenesis that may indicate gonadectomy. There is a useful review of tumours arising in dysgenetic gonads and summary of management of patients with 46XY gonadal dysgenesis.     

Morphology of the genitals in gonadal dysgenesis

The entity includes the Turner syndrome, the pure gonadal dysgenesis (Swyer syndrome), the asymmetrical gonadal differentiation, and gonadal dysgenesis of some forms of trisomy. The necessity of prophylactic gonadectomy in all patients with Y chromosome is stressed because of a close association with the arising of tumors in the dysgenetic gonads. The requirements are described of a successful substitution with steroids.     

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.     

The coincidence of gonadal dysgenesis and hyperprolactinemia

It was reported about 6 female patients aged from 3 to 31 years (average age 18 years) with gonadal dysgenesis and hyperprolactinemia. Beside one all these females were not treated with synthetic sexual steroids. In 5 of the 6 patients both hyperprolactinemic and hypergonadotropic serum levels were observed. In one case the gonadotropic serum levels were normal. In 4 patients a stimulation test with GRH-TRH or Arg-GRH-TRH, respectively, was performed. In patients with gonadal dysgenesis a change on the area of the hypothalamic-hypophyseal axis is supposed to cause the hyperprolactinemia.     

Olfactory, auditory, and gustatory function in patients with bonadal dysgenesis.

The olfactory, auditory, and gustatory functions of 20 women with gonadal dysgenesis were studied. Various abnormalities of these functions were found, and they occurred principally in patients with mosaicism of the sex chromosomes. This is further evidence of the increased likelihood of various somatic abnormalities among women with gonadal dysgenesis, and particularly among those who carry more than one line of sex chromosomes.     

Features of pubescence in patients with pure gonadal dysgenesis in the course of a hormonally active tumor--case report

Germ cell tumors are the most frequent ovarian neoplasms among girls and young women under the age of 25. Female patients with gonadal dysgenesis are at higher risk of germ cell tumors. Two cases of women with pure gonadal dysgenesis were described. A hormonally active tumor secreting estrogens, caused the development of sexual features and genital tract bleeding what imitated premature puberty. It needs to be emphasized that the presence of sexual features does not exclude dysgenesis - a pathology that is connected with an increased risk of gonadal tumors--and that the ultrasound evaluation, during which the presence of follicles in gonads is evaluated, is essential.     

Epithelial ovarian carcinoma in patients with intersex disorders: The role of pituitary gonadotropins in ovarian tumorigenesis

The common epithelial tumors of the human ovary have rarely been found in the gonads of intersex patients with gonadal dysgenesis or true hermaphroditism. This report describes a patient with ovarian serous cystadenocarcinoma and mixed gonadal dysgenesis (45,X/46,XY) and reviews other reported cases. Intersex patients require early evaluation with treatment based on the karyotypic risk of malignant gonadal transformation. Epithelial ovarian tumors arising in dysgenetic gonads, which lack ova and are incapable of ovulating, provide a unique model for understanding the role of pituitary gonadotropins in ovarian epithelial tumorigenesis.     

Familial 46,XY pure gonadal dysgenesis and gonadoblastoma/dysgerminoma: case report

The case reports of two sisters admitted for evaluation of primary amenorrhea are presented. Gynecological and endocrinological investigations and chromosomal analysis led to the diagnosis of familial 46,XY gonadal dysgenesis. Both sisters underwent bilateral salpingo-oophorectomy and hysterectomy. Histological examination revealed dysgenetic gonads with gonadoblastoma and dysgerminoma. Five years after treatment by surgery and irradiation the patients are well and free of recurrence. These cases again confirm the risk of malignancy and the necessity of prophylactic gonadectomy in all patients with gonadal dysgenesis and Y chromosomal material.     

The importance of determining karyotype in premenarchal females with gonadal dysgerminoma: two case reports

Abstract. Gonadal dysgerminomas developed in two girls, aged 12 and 15 years. Both were initially treated with conservative unilateral gonadectomy. Forty-six, XY gonadal dysgenesis was not suspected in either patient due to the normal appearance of the contralateral gonads and internal female genital organs. One died of a second germ cell malignancy which developed in the contralateral ovary 9½ years later. The diagnosis of 46, XY gonadal dysgenesis was established by karyotype in both patients. Although conservative surgical management is desirable for nulliparous women with unilateral dysgerminomas, the presence of 46, XY gonadal dysgenesis should be suspected in all premenarchal girls with ovarian germ cell malignancies. If karyotyping reveals the presence of an Y chromosome, bilateral gonadectomy is indicated because of the risk that another neoplasm may develop in the contralateral ovary.     

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.     

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.     

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.     

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.     

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.     

Azoospermie et mosaïque 45,X/46,XY : à propos d’un cas

Chromosomal abnormalities are common in patients with oligozoospermia or azoospermia. We report the case of a 32-year patient, with male phenotype, and without hormonal or morphological abnormalities, with a severely reduced spermatogenesis. It was revealed a 45,X/46,XY gonadal dysgenesis. We have reviewed the various problems inherent in the discovery of this rare gonadal dysgenesis, including genetic, cancer and fertility risks.