Assessment of the role of laparoscopic ovarian biopsy.

Seventy-four patients with either endocrine and/or infertility problems were subjected to laparoscopic ovarian biopsy. The patients were divided into 4 categories: those with primary amenorrhea, secondary amenorrhea, ovarian androgenic hyperfunction, and infertility. The results were critically examined to evaluate the procedure in the investigation and treatment of each of these disorders. It was concluded that laparoscopic ovarian biopsy is most helpful in primary amenorrhea but justified in secondary amenorrhea only if a histologic diagnosis of premature ovarian failure is though to be essential. Patients with ovarian androgenic hyperplasia should not be candidates for the procedure as the laparoscopic appearance of the ovaries offered equally valuable information and the hazards of biopsy in this particular group of patients outweighed its diagnostic and therapeutic usefulness. The ovarian biopsy offered very little benefit for the infertility patients.     

The genetics, diagnosis and treatment of amenorrhea

The menstrual cycle is regulated by complex feedback interactions between the ovaries, pituitary and hypothalamus. A disruption at any point in one of these pathways may lead to irregularities in the menstrual cycle. In particular, amenorrhea, the cessation of menstrual functioning, serves as an indicator of ovarian, pituitary and/or hypothalamic dysfunction. Historically, diagnosing and treating amenorrhea presented medical professionals with numerous practical difficulties. In recent years, however, studies of amenorrhea have yielded new understandings and new treatments of the disorder. This paper synthesizes these current methodologies for diagnosing, treating and understanding both primary and secondary amenorrhea.     

Long-term clinical effects of ovarian wedge resection in polycystic ovarian syndrome

Twenty-nine consecutive patients with polycystic ovary (PCO) syndrome (defined as hirsutism plus oligomenorrhea or secondary amenorrhea, and excluding Cushing's syndrome, an androgen-secreting adrenal or ovarian tumor or adrenocortical hyperplasia) were treated with ovarian wedge resection leaving normal-sized ovaries. Long-term follow-up from 2.3-9.5 years (mean 5.7 years) showed that 26 of 29 patients (90%) had established normal menstrual cycles. Fertility and normal pregnancies were achieved in all 10 patients (100%) with normal postoperative menstrual cycles who desired to conceive, but not in the 3 patients with remaining postoperative oligomenorrhea. Eight of 9 patients who were obese preoperatively and who had normal postoperative menstrual cycles showed a major weight loss after wedge resection. In contrast, none of the preoperatively obese patients, who remained oligomenorrheic after surgery, lost weight. Hirsutism was not cured by wedge resection. It is concluded that ovarian wedge resection should still be considered useful in patients with PCO.     

Hormonal disorders,menstrual irregularities and future fertility

Menstrual irregularities are common in puberty and adolescence during the development of ovarian function and until a regular ovulatory cycle is established. Hormonal disorders should be investigated promptly to avoid or alleviate possible long-term sequelae, including impaired fertility. Most irregularities are transient and self-limited, but some are severe or prolonged and require exploration and treatment. Symptoms such as prolonged oligomenorrhea andoligoamenorrhea may herald an incipient or preexisting endocrinopathy. An exact diagnosis by estimation of the hormonal parameters can identify a relevant disturbance. The prognosis for later fertility in patients with oligoamenorrhea depends on the etiology and degree of the condition. With a hypothalamic origin the prognosis is good when the offending stimuli are removed. Patients with pituitary lesions or hyperprolactinemia can be treated effectively. Hyper-androgenemic oligoamenorrhea, especially the polycystic ovarian syndrome, are common. Future fertility is reduced but may be improved by preventive measures and therapy in adolescence. Inpatients with primary ovarian insufficiency and persisting hyper-gonadotropic amenorrhea, the prognosis for fertility is poor.     

Correlation of the ultrasonic appearance of the ovaries in polycystic ovarian disease and the clinical, hormonal, and laparoscopic findings

The ovarian ultrasonic appearance in 20 patients with polycystic ovarian disease was studied and correlated to the clinical, hormonal, and laparoscopic findings. Ultrasound studies showed that both ovaries were enlarged in 15 patients (15.46 +/- 2.5 cm3). Maximum ovarian surface area was 9.75 +/- 3.38 cm2. Three ultrasonic patterns were detected: (1) isoechoic, with no discernible cysts (four patients); (2) hypoechoic, with multiple small cysts of less than 1 cm (11 patients); (3) hypoechoic, with single cyst of greater than 1 cm (five patients). Ultrasonic estimation of ovarian size was superior to clinical assessment and equal to that of laparoscopic examination. Subtle differences existed between the ultrasonic appearance of the ovaries in hyperprolactinemic subgroups of polycystic ovarian disease compared to normoprolactinemic ones. However, no significant relationship was found between the ovarian size and any of the hormones studied. Obesity, amenorrhea, hirsutism, hyperprolactinemia, and elevated testosterone and dehydroepiandrosterone sulfate levels were more common in the group with enlarged ovaries, whereas oligomenorrhea, elevated luteinizing hormone/follicle-stimulating hormone ratio, and elevated androstenedione and estrone levels occurred more frequently in the group with normal-sized ovaries. The value of ultrasound studies in the management of polycystic ovarian disease is emphasized.     

Resistant ovary syndrome. Case report

Patients with primary amenorrhea, sexual infantilism and elevated pituitary gonadotropins are frequently diagnosed with hypogonadism hypergonadotropic and suspected ovarian failure, secondary to a chromosomal abnormality, intrinsic ovarian failure or altered receptors for gonadotropins, mainly FSH (ovarian resistance). We report the case of a 16-year-old, admitted to the endocrinology clinic for primary amenorrhea and lack of development of secondary sexual characteristics. A complete physical examination revealed: height of 1.58 m and 57 kg weight, with incipient breasts (Tanner I), sparse pubic and axillary hair (Tanner I). The ultrasound reported small uterus and ovaries. Laboratory studies reported high levels of FSH and LH, estradiol and testosterone levels before puberty, prolactin, TSH, T3 and T4 normal. Normal female karyotype. Diagnostic laparoscopy was performed which showed two ovarian slips; biopsy was taken and reported both abundant primordial follicles and spindle cell stroma without evidence of primary and antral follicles, which integrates the diagnosis of resistant ovary syndrome.     

Luteinizing hormone-releasing hormone (LH-RH) as a diagnostic and research tool in gynecologic endocrinology

A study is reported on the effects of 150 mcg. of luteinizing hormone-releasing hormone (LH-RH), administered iv to 48 women with 5 types of secondary oligoamenorrhea, on the serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) Levels. At Time 0, patients with pituitary disease showed a markedly diminished LH response and patients with polycystic ovarian disease with enlarged ovaries showed a brisk, elevated LH response. FSH levels in patients with pituitary disease and polycystic ovarian disease showed a negligible rise at Time 0. 9 of 10 patients with pituitary disease and 5 of 9 patients with dietary amenorrhea had a low LH response 30 minutes after LH-RH administration. FSH response 60 minutes after injection in patients with pituitary disease and polycystic ovarian disease seemed to be lowered though too much overlap prevented a complete diagnosis. The conclusion of this initial study is that through baseline determinations of FSH and LH, along with a LH-RH stimulation test, useful data are provided for determining whether amenorrhea is due to ovarian or pituitary failure. A 2nd study evaluated the effects of 150 mcg of LH-RH administered iv before and after the im administration of various dosages of estrogen and progesterone to anovulatory women. A vigorous response in pituitary gonadotropin, particularly LH, was observed with LH-RH administered only. The effect with estrogen and progesterone was diminished pituitary response in terms of LH production. It is concluded that estrogen and progesterone exert a negative feedback effect on gonadotropin secretion at the hypothalamic and pituitary levels.     

Premature ovarian failure

The diagnosis of premature ovarian failure was made in 35 women (ages 17 to 40) with increased concentrations of follicle-stimulating hormone and luteinizing hormone. Three had primary amenorrhea, 29 had secondary amenorrhea (less than one to 15 years), and three had irregular menstrual intervals of less than six months. Symptoms and signs of estrogen deficiency were present in fewer than 50% of these women and were not helpful in distinguishing the different causes of ovarian failure. Six of these women had an autoimmune disorder associated with ovarian failure. Thirteen of 16 women had a normal 46,XX karyotype, and five of 14 women who had an ovarian biopsy had a specimen that contained follicles with oocytes. Two women conceived after they developed ovarian failure and while taking cyclic estrogen and progestin.     

Gonadal dysgenesis and Rokitansky syndrome. A case report.

BACKGROUND: Primary amenorrhea and lack of sexual development occur in gonadal dysgenesis due to missing ovaries. Primary amenorrhea with sexual development occurs in Rokitansky syndrome due to absence of the uterus, with normal ovarian function. The association of these two conditions has been previously described as a rare event. CASE: A 19-year-old woman presented with primary amenorrhea and lack of secondary sexual characteristics. Physical examination confirmed the absence of mammary development and of pubic and axillary hair. Pelvic ultrasound disclosed absence of the uterus and ovaries. Gonadotropin serum levels were in the menopausal range, and the karyotype showed two mosaic cell lines, 45,X/46,Xdic(X). Scanning of a large number of cells by interphase fluorescence in situ hybridization showed 12% of cells with a dicentric X chromosome. Laparoscopic study confirmed the absence of the uterus and ovaries, with normal fallopian tubes. CONCLUSION: This patient had two anomalies affecting reproductive performance, gonadal dysgenesis and congenital absence of the uterus, the first associated with an abnormal karyotype; the second seems to have occurred coincidentally. At this time there is no treatment for the reproductive dysfunction.     

Ovarian follicular apparatus and hormonal parameters in patients with primary and secondary amenorrhea.

Correlation between ovarian follicular apparatus and hormonal parameters such as serum gonadotropin and urinary estrogen levels was investigated in patients with primary and secondary amenorrhea. Serum gonadotropin levels were elevated in amenorrheic patients without ovarian follicles or with follicles of low developmental stage and pituitary responsiveness to LH-RH in these patients were marked compared with patients with follicles of high developmental stage or normal ovulating women in the follicular phase of the menstrual cycle. The 24-hour urinary excretion of total estrogens was low in patients without follicles or with follicles of low developmental stage and ovarian responsiveness to exogenous gonadotropins was quite low in comparison with patients with highly developed follicles or normal control subjects. Thus, serum gonadotropin and urinary estrogen measurements and LH-RH and gonadotropin loading tests are diagnostic of the presence or absence and the state of development of ovarian follicles in the diagnosis and treatment of primary and secondary amenorrhea.     

24-year-old female with amenorhea: bilateral primary ovarian Burkitt lymphoma

OBJECTIVES: Burkitt's lymphoma (BL) occurs mostly in children. Isolated bilateral ovarian involvement presenting with amenorrhea is extremely rare in young adults. CASE: A 24-year-old female presented with secondary amenorrhea. Bilateral adnexal masses were identified on physical examination and abdominal computed tomography (CT). She underwent total abdominal histerectomy and bilateral salpingoophorectomy. Histopathologic evaluation yielded a diagnosis of BL of ovaries. Combined chemotherapy was administered. After complete remission an autologous bone marrow transplantation (ABMT) was performed. She died 35 days after ABMT. CONCLUSIONS: Although rare, BL should be kept in mind when isolated ovarian tumors are detected in young patients.     

Hypothalamische Ovarialinsuffizienz

The regulation of ovarian function requires complex interactions between hypothalamus, pituitary, and ovaries. Ovarian insufficiency is defined as a failure in ovarian function followed by inappropriate oocyte maturation associated with endocrine deficits and dysfunctions. Ovarian failure represents, independent of its primary cause, a pathophysiological continuum ranging from corpus luteum insufficiency, polymenorrhea, and anovulatory cycles to oligo- and amenorrhea. The appearance of these symptoms therefore makes the exact clarification of a possible differential diagnosis necessary. In contrast to a complex classification of ovarian failure into seven different groups with subgroups, suggested by the WHO in 1976, in clinical practice, we divide the classification of ovarian dysfunction into four groups, namely: hyperandrogenemic, hypothalamic, hyperprolactinemic, and primary ovarian insufficiency. This review focuses on hypothalamic ovarian failure.     

Pregnancies in primary amenorrhea with normally developed secondary sex characteristics

We report herein 11 pregnancies in patients with primary amenorrhea and normally developed secondary sex characteristics. All patients were fully investigated, and their ovaries as visualized by laparotomy or laparoscopy were found to be small. Ovarian biopsy revealed numerous unstimulated primordial follicles. The hormonal profiles showed hypoestrogenism with atrophic endometrium. Human gonadotropins were used in large amounts in order to achieve pregnancy. Two patients responded in all treatment cycles with menses. The remainder failed to respond to all treatment cycles. All patients became pregnant and carried their pregnancies normally to term. There were four sets of twins and seven single births. Of fifteen newborns, one died of congenital heart disease.     

Pregnancy associated with hypergonadotropic hypogonadism.

A case of a 30-year-old female with secondary amenorrhea and relative hypergonadotropic hypogonadism is presented. The patient demonstrated persistently elevated levels of gonadotropins in spite of clinical and laboratory evidence of estrogen production. Laparoscopic directed biopsy revealed a total absence of ova, but in spite of this finding, conception ensued. Variations in ovarian sensitivity throughout the female reproductive period and in certain pathologic states are discussed, as well as the apparent limitation of single laparoscopic directed biopsies for confirming the diagnosis of premature menopause. Finally, the theoretical use of exogenous estrogen to induce ovulation in patients with the ovarian insensitivity syndrome is discussed.     

The gonadotropin-resistant ovary syndrome in association with secondary amenorrhea.

A young patient with secondary amenorrhea and primary infertility is described. After a gynecological-endocrinological exploration including laparoscopy, the diagnosis indicates secondary hypergonadotropic, hypo-estrogenic normo-androgenic amenorrhea. The anatomopathological examination of an ovarian biopsy revealed an intact follicular apparatus, thus disproving the suspected diagnosis of climacterium praecox. Since very high gonadotropin doses could not induce an ovulation, it was concluded that the rare combination of secondary amenorrhea and the gonadotropin-resistant ovary syndrome must be present. The pathogenesis of this syndrome is discussed.     

The therapeutic value of low-dosage irradiation of the pituitary gland and ovaries in functional menstrual disorders and sterility

Low-dosage irradiation of the pituitary gland and ovaries resulted in restoration of the menstrual function in 59 per cent of 106 cases of amenorrhea, 89 per cent of 18 cases of dysfunctional metrorrhagia during the childbearing age and in 57 per cent of 26 cases of dysfunctional menorrhagia. It had no effect in 3 cases of hypomenorrhea. The amenorrhea of 2 patients was presumably aggravated by the treatment.Low-dosage irradiation of the putuitary gland and ovaries in 26 women with normal menstrual cycles resulted in temporary amenorrhea of one who, however, had in the past shown a tendency to amenorrhea.Low-dosage irradiation of the pituitary gland and ovaries is highly effective in sterility of women with functional menstrual disorders but has very little, if any, effect in those who menstruate normally.     

Synchronous primary neoplasms of the uterine corpus and the ovary: a case report

OBJECTIVE: To determine the frequency of synchronous primary neoplasia of the ovaries in patients with primary malignant neoplasia of the uterus, and to analyze the clinical and histological characteristics of these cases. MATERIALS AND METHODS: Clinicopathological data from a series of patients treated for primary malignant neoplasia of the uterus between 1985 and November 2003 have been studied retrospectively. RESULTS: Synchronous primary neoplasia of the ovaries was found in 13 out of 173 patients (7.5%) treated for primary malignant neoplasia of the uterus. In four patients (2.3%) the histological findings suggested ovarian metastases from primary endometrial adenocarcinoma. In four other cases (2.3%) there was extension of the primary uterine sarcoma to the ovaries. In the remaining five cases (2.9%) primary endometrial adenocarcinoma coexisted with: a) ovarian cystadenocarcinoma in two cases, b) ovarian fibromathecoma in two cases, and c) ovarian tumor of borderline malignancy in one case. CONCLUSIONS: Coexistence of distinct primary neoplasias in the uterus and ovaries is rare. Diagnosis of two primary malignancies in the uterus and ovaries should be based on histological examination. Treatment should be appropriate for both tumors, taking into consideration that treatment of one tumor will not lead to subtreatment of the other.     

Etiology, clinical features and prognosis in secondary amenorrhea.

A clinical investigation of 356 patients with secondary amenorrhea revealed that 95% of patients with postpill amenorrhea and 56% of patients with anorexia nervosa recovered in 6 years. The corresponding recovery rates for patients with psychogenic amenorrhea and amenorrhea following self-induced weight loss were 72% for both groups, and in patients with the amenorrhea-galactorrhea syndrome and idiophatic functional amenorrhea the recovery rates at 6 years were 64 and 61% respectively. Unlike the other groups with functional amenorrhea, patients with the amenorrhea-galactorrhea syndrome had impaired ovarian responsiveness to exogenous gonadotropins. Bromocriptine treatment resulted in disappearance of the galactorrhea and restoration of the menses and/or ovulation in nine of 18 patients; of these three became pregnant. The effect of bromocriptine did not persist for long after treatment ceased, and permanent recovery was recorded only in four patients. The group with functional amenorrhea included 34 patients who wished to become pregnant. Gonadotropin treatment was successful in 20 patients, clomiphene-hCG in two, tamoxifen in two, bromocriptine in two, and combined bromocriptine and clomiphene in one. Thus, the overall pregnancy rate in patients with functional amenorrhea was 79%. The groups with ovarian amenorrhea inclutients with assumed ovarian failure responded to large doses of exogenous gonadotropins by ovulation and three became pregnant. Ovarian wedge resection was ineffective in all five cases with polycystic ovaries, but two patients became pregnant after treatment with clomiphene and chorionic gonadotropin, and one with exogenous gonadotropins.     

月经紊乱患者的细胞遗传学分析

目的 分析原发闭经、继发闭经及月经稀发患者的染色体核型,探讨性染色体异常对性腺发育的影响。方法 将176例患者分为两组,其中82例原发闭经组,94例继发闭经及月经稀发组。每例行外周血培养,制片及G显带,并行染色体核型分析。结果 176例患者发现性染色体异常38例,异常检出率为29.6％(38/176),其中原发闭经组33例,异常检出率为40.2％(33/82);继发闭经及月经稀发组检出性染色体异常5例,异常检出率为5.3％(5/94);两组异常检出率差异有显著性(P<0.05)。性染色体异常大体上分为三大类:含Y染色体(15例),X染色体数目异常(18例),X染色体结构异常(5例),嵌合体均以45,X系为主,共10例。结论 两条完整的染色体是女性性腺发育及正常卵巢功能所必须,性染色体异常是原发闭经的主要原因之一,常规细胞遗传学检查是必要的;继发闭经及月经稀发也不应忽视此项检查。     

Inguinal pelviscopy. A new approach for examining the pelvic organs

Inguinal pelviscopy is a new approach for examining structures in the extra- and intraperitoneal pelvic cavity. The total number of patients studied was 70. The method was used to visualize and take biopsies from masses in the presacral area (3 patients) and in the ovaries (8 patients). Ovarian biopsies were taken from 26 patients (14 with primary amenorrhea and 12 with elevated follicle-stimulating hormone), and ovarian cyst aspiration and biopsy were performed in 12 patients. Tubal sterilization was done in 18 cases and lysis of pelvic adhesions in 3 infertile patients. The procedure comprises entry of the extraperitoneal pelvic cavity through the inguinal canal. Intraperitoneal pelvic cavity examination can also be done by piercing the peritoneum at the deep inguinal ring or close to the fallopian tube. No complications were encountered except urinary retention in 1 patient with presacral tumor and abdominal wall hematoma in another patient. The approach is safe, direct and easy. It is performed on an outpatient basis.