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[Tests of adrenal gland and ovarian function in the hyperandrogenemia syndrome].
Androgen production in women is under the influence of pituitary hormones on ovaries and adrenal glands, or they originate from peripheral conversion of androgen precursor. Each of the three principal compartments of androgen production has a serum specific marker that may be clinically helpful. Serum testosterone signifies ovarian production, dehydroepiandrosterone sulfate (DHA-S) is an adrenal marker, and serum 3 alpha-diol glucuronide reflects androgen action in the peripheral compartment. Many physiologic and pathologic states affect transport proteins and enzyme systems which modulate androgenic activity. This fact makes the determination of mechanism and origin of hyperandrogenemia more difficult, as well as the choice of therapy. In the syndrome of hyperandrogenemia, the primary place of the disorder is determined by the tests of adrenal cortex and ovary functions. The correct response of androgens in dexamethasone test is manifested by free testosterone suppression to < 0.028 nmol/L, and by DHA-S and plasma cortisol suppression under the reference values. In the complex and controversial syndrome of hyperandrogenemia, the nafarelin test is used after insufficient free testosterone suppression in dexamethasone test. The significant diagnostic criterion is the rise of 17-hydroxyprogesterone (17-OHP) over 7 nmol/L, which aligns a great number of idiopathic hyperandrogenemias in the group of polycystic ovary syndrome. A good correlation was found between the rise of 17-OHP in nafarelin test and the suppression of free testosterone in dexamethasone test. This finding supports the conception that both tests determine the ovary function and that their sensitivity and specificity for ovary hyperandrogenemia is comparable.
[Citric acid as possible function test; relation between the elimination of citric acid and ovarian function].
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The study of ovarian artery hemodynamics in patients with infertility by color Doppler energy.
Seventy-four cases of infertility were examined to study the hemodynamics of the bilateral ovarian arteries at 21st day during the corpus luteum phase by color Doppler energy(CDE) and color Doppler flow imaging (CDFI). All the patients were verified by laparoscopy, fallopian tube patency examination and ovarian function test. Twenty-two healthy women served as controls. The results showed that the difference of resistance index(RI) and pulsatility index (PI) of bilateral ovarian arteries between the infertility and the normal controls had statistical significance (P < 0.01), and the PI showed negative correlation with the thickness of endometrium (left side: r = 0.724, P < 0.01; right side: r = 0.756, P < 0.01). The results also showed that CDE was more sensitive than CDFI in displaying the ovarian arteries. It could be concluded that the elevated resistance of ovarian artery during the corpus luteum phase was one of the important factors that resulted in infertility.
Transient liver function tests abnormalities in ovarian hyperstimulation syndrome.
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Assessment of ovarian reserve: is there still a role for ovarian biopsy in the light of new data?
Ovarian reserve depends on the number of primordial follicles in the ovarian cortex. It was suggested that determining the follicular density directly by obtaining ovarian biopsy might be more accurate than current indirect biochemical and ultrasonic tests, especially for women in the later stage of their reproductive life. It might also be important and beneficial for young patients having chemotherapy for malignant disease in whom the ovarian tissue should be considered for reimplantation after recovery. The advantages and pitfalls of obtaining ovarian biopsy in these cases are discussed in light of new emerging data on the natural distribution of primordial follicles in the human ovary and its implications.
Clomiphene citrate challenge test in the assessment of ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection.
The objective of this study is to evaluate the performance of clomiphene citrate (CC) challenge test to predict diminished ovarian reserve before controlled ovarian hyperstimulation for intracytoplasmic sperm injection (ICSI). The 198 women who underwent the CC challenge test fulfilled the following criteria; over 35 years of age, removal of one ovary or previous ovarian surgery, the presence of ovarian endometrioma or previous poor response to ovarian hyperstimulation. Of the patients tested, 141 were found to have a normal CC challenge test while 57 had an abnormal result. The cancellation rate of the cycle with a poor response was significantly higher in women with an abnormal test (36.8%) than in those with a normal test (19.8%) (P < 0.05). The sensitivity of CC test for cycle cancellation was found to be 43% with a specificity of 76%, positive and negative predictive values of 37 and 80%, respectively. The estradiol values on hCG day, the number of retrieved oocytes and metaphase II oocytes and the rate of transfer cycles were significantly lower in females with an abnormal test. Women with normal test results had higher pregnancy rates per embryo transfer than those with abnormal test results (21.5 vs. 13.3%) and the predictive value of an abnormal test for failing to conceive was 93% (53/57) with a sensitivity of 31%, specificity of 84% and negative predictive value of 15.6%. Of 57 women with an abnormal test result, 25 (43.8%) were abnormal due only to an elevated day 10 or 11 value of FSH, which could not be detected using only basal FSH screening. In this group, the cancellation rate (48 vs. 19.8%, P < 0.01), the rate of transfer cycles (48 vs. 72.3%, P < 0.05) and the mean number of retrieved oocytes (4.9 +/- 2.5 vs. 6.4 +/- 3.1, P < 0.01) were all significantly different from normal test group. Although the rate of pregnancies per started cycle (8 vs. 15.6%) did not show a statistically significant difference, this is most probably due to the low number of patients. In conclusion, an abnormal CC challenge test is a good predictor of diminished ovarian reserve and it is better than a basal FSH concentration on day 3. It provides valuable information for both patients as to their chances of achieving a pregnancy and also for the medical team deciding on options for stimulation protocols.
Premature ovarian failure.
PURPOSE OF REVIEW: To summarize current knowledge about premature ovarian failure (POF) with an emphasis on recent developments regarding its management. RECENT FINDINGS: The incidence of POF is increasing largely due to improved survival rates of cancer patients treated with radiation and chemotherapy. Delayed diagnosis and management of POF leads to suboptimal outcomes. Anticipation and early detection of this condition in high-risk women by means of ovarian function testing, followed by early institution of appropriate management could improve outcomes. Choice of strategies should vary depending on the age of onset, associated symptoms and fertility aspirations of the individual, and should change with the patient's advancing age. SUMMARY: Early assessment of the individual's risk of developing POF, development of a strategic management plan, and timely commencement of infertility and hormone deficiency treatment, together with counselling in an integrated management plan should improve both the short and long-term health of those with POF.
Variations in the molecular forms of prolactin during the menstrual cycle, pregnancy and lactation.
Size heterogeneity of immunoreactive prolactin (PRL) was studied in serum samples obtained from eight normoprolactinemic women during the menstrual cycle and five additional patients at pregnancy and lactation. Gel filtration of sera from women with normal ovarian function tested at day 10-12th of their menstrual cycle showed two predominant PRL forms, approximately 22K and 26K mol wt. In addition two polymeric variants, 50K ("big" PRL) and 100K ("big-big" PRL) were found in less proportion, accounting for approximately 34% of the total PRL immunoreactivity detected in the sera. It was also noted a low mol wt form eluting around the region of 16K mol wt. In pregnant women the major PRL form was the 22K and its proportion showed a gradual increase as progression of gestation. The polymeric PRL forms were found in substantially less amount as gestation progressed. After parturition, in nursing mothers the 22K form remained prominent and in greater concentrations than the 26K monomeric variant. Large and low mol wt PRL forms were constantly detected in sera from women during the lactation period. From these data we confirmed that PRL circulates at various molecular forms and the relative proportion of these molecular variants exhibit changes according to the physiological state. In our study the predominant form was the 22K PRL (nonglycosylated) and it was of interest to discover the presence of a low mol wt PRL which elutes in the 16K area. The significance of this latter finding is not clear at the present.
Ovarian neoplasias in children.
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[Preserving ovarian function in the treatment of epithelial and special (other) malignant ovarian tumors].
About 90% of malignant tumors of the ovary in Scandinavia develop from the germinal epithelium. There are great differences in the incidence rates between countries in the Western world and in Africa and Asia. The WHO classification of ovarian malignancies is generally used. The epithelial tumors comprise the serous, mucinous, endometrioid, clear cell, undifferentiated and mixed true carcinomas. In addition, borderline lesions of especially the serous and mucinous types are of interest when the question of preservation of ovarian function comes into notice. Conservative surgery, which means removal of only the afflicted ovary should be restricted to young women of the childbearing age who want to preserve the possibility of becoming pregnant. However, certain prerequisites must be fulfilled. The tumor must be located to one ovary only (Stage Ia) and must be either a borderline lesion or a Grade 1 true carcinoma of either the serous, mucinous or endometrioid type. There must be no ascites and peritoneal washings must be negative for cancer cells. Germ cell tumors are usually found in young women. Only the dysgerminomas are regularly bilateral in 10-15% of the cases. All other germ cell tumors are rarely bilateral. But both in borderline lesions, Grade 1 true carcinomas, and in germ cell tumors, a biopsy of the normal looking contralateral ovary should always be performed. Endodermal sinus tumors and immature teratomas may well be treated conservatively by surgery, but modern triple chemotherapy (VAC, PVB) must be added. Granulosa theca cell tumors are bilateral in only about 5% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Fertility preservation options for women with malignancies.
UNLABELLED: Cancer is not rare in younger women. There has been a remarkable improvement in the survival rates due to progress in cancer treatment. The necessary treatment for most of the common cancer types occurring in younger women implies either removal of the reproductive organs or cytotoxic treatment that could partially or definitively affect reproductive function. Early loss of ovarian function not only puts the patients at risk for menopause-related complications at a very young age, but is also associated with loss of fertility. Further, women in the western hemisphere have been delaying initiation of childbearing to later in life. The results of these changes have led to an increase in patients facing the risk of premature ovarian failure, and therefore seeking help in preserving their fertility. This increase in demand has resulted in a proliferation of techniques to preserve fertility. Indeed, the number of options is increasing; some are more established procedures, such as embryo cryopreservation, and some are still experimental, such as ovarian cryopreservation. Because of the variations in type and dose of chemotherapy, the type of cancer, the time available before onset of treatment, the patient's age and the partner status, each case is unique and requires a different strategy of fertility preservation. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the potential early loss of ovarian function secondary to radiotherapy and/or chemotherapy for cancer at a young age; explain the increasing demands for fertility preservation; and summarize the limited number of proven, safe, and efficacious methods.
The role of ovarian ablation in the management of breast cancer.
In recent years the role of ovarian ablation as a therapeutic modality not only in the prevention but also in the treatment of breast cancer has reemerged after its initial use more than a century ago. BRCA-1 and BRCA-2 mutation carriers have an 85% lifetime risk of developing breast cancer. Bilateral salpingo-oophorectomy is effective in reducing the risk of developing breast cancer in both BRCA-1 and BRCA-2 mutation carriers by 50%. Tamoxifen reduces the risk of breast cancer in BRCA-2 mutation carriers, but not in BRCA-1 mutation carriers. Breast cancer arising in BRCA-1 mutation carriers is often estrogen receptor (ER) negative, unlike breast cancer developing in BRCA-2 mutation carriers. Sixty percent of premenopausal patients with breast cancer have ER-positive disease and 25% of breast cancer patients are premenopausal at diagnosis. The Early Breast Cancer Trialists' Collaborative Group review has shown ovarian ablation to be an effective adjuvant therapy for premenopausal breast cancer patients less than 50 years of age. But the Early Breast Cancer Trialists' overview also shows the benefit of ovarian ablation is uncertain if these patients also receive chemotherapy. Does the overview underestimate the efficacy of ovarian ablation? Some patients in these trials were ER negative. Most women less than 50 years of age who receive adjuvant chemotherapy become menopausal. So there is a need to test ovarian function suppression in the group who can benefit, or in other words, those that remain premenopausal after chemotherapy and have endocrine responsive breast cancer.
[Jayle's test for the ovarian function investigation].
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Ovarian function after autologous bone marrow transplantation.
PURPOSE: To determine the frequency of return of ovarian function after autologous bone marrow transplantation (ABMT), and the major factors that predict recovery. PATIENTS AND METHODS: Records of 200 consecutive women who underwent ABMT at the University of Toronto Autologous Blood and Marrow Program (Toronto, Canada) were reviewed. Seventeen patients met the inclusion criteria, which were (1) alive at the time of evaluation, (2) disease-free at least 18 months after transplantation, (3) age younger than 50 years at transplantation, and (4) premenopausal before transplantation. Recovery of ovarian function was determined by pregnancy or regular menses, with no menopausal symptoms and an estradiol level greater than 20 pmol/L off hormonal therapy. RESULTS: All 17 patients became menopausal immediately after ABMT. Five patients (29%) recovered ovarian function a median of 24 months post-ABMT (range, 6 to 48 months). The median age at transplantation of women with restored ovarian function was 19 years (range, 19 to 28 years) versus 30 years (range, 22 to 48 years) for those who did not regain function. Younger age at transplantation predicted ovarian recovery (P = .03) by means of a log-rank test. Only one of five women who regained ovarian function received total-body irradiation (TBI) compared with five of 12 women who did not. Univariate analysis suggested a trend for TBI to predict a sustained loss of ovarian function (P = .067). The number of regimens of induction or salvage chemotherapy that contained an alkylating agent ranged from none to five and was not predictive (P = .45). CONCLUSION: All women became menopausal after ABMT but 29% recovered ovarian function. Younger age at transplantation predicted return of ovarian function, whereas TBI may have had a negative effect.
Assessment of ovarian reserve. Is there still a role for ovarian biopsy? First do no harm!
Multiple endocrine, ultrasound-based and dynamic tests have been proposed for the assessment of ovarian reserve. Lately, ovarian biopsy has been proposed as a more representative functional test of ovarian reserve, and has been recommended as an early step in the investigation of infertility. Central to this hypothesis is the idea that a random biopsy of the ovarian cortex is reflective of the actual ovarian follicular pool. Recent studies have shown a wide variation in the number and distribution of ovarian follicles even from the same ovary and in the same patient. Coupled with the invasiveness of performing the biopsy and the risk of adhesion formation, we believe that there should not be a role for ovarian biopsy in ovarian reserve testing.
[Use of the clomiphene test for evaluation of the functional state of the hypothalamus-pituitary gland-ovarian system in ovarian hyperandrogenia].
The authors studied the content of gonadotropins and testosterone in the blood; functional condition of the hypothalamus-hypophysis-ovarian system was characterized in patients with ovarian hyperandrogenia by using the klomiphen test. Testosterone level in all the patients and prolactin level in 70% of the patients proved to exceed the normal values, wheras the LH level could be low, normal or high. With klomiphen test it was shown that both the gonadotropin and estrogen levels rose against the background of action of the preparation; as to testosterone level--it remained unchanged. In induced menstrual cycles estradiol peak preceded the gonadotropin peak. In patients with ovulation testosterone level diminished by the end of the observation period.
An unusual case of ovarian resistance syndrome.
BACKGROUND: Women who present with elevated gonadotropins, primary amenorrhea, and sexual infantilism usually have an abnormal karyotype or premature ovarian failure. We describe a rare case of ovarian resistance secondary to a gonadotropin post-receptor defect. CASE: An 18-year-old presented with amenorrhea and sexual infantilism. Original workup led physicians to believe the patient had uterine agenesis with premature ovarian failure. Ovarian biopsy proved the presence of follicles. After 48 months on hormone replacement, the patient went through the stages of puberty, including menarche. Re-evaluation proved the presence of a uterus. CONCLUSION: Ovarian resistance is a rare cause of hypergonadotropic hypogonadism. With this type of ovarian dysfunction, women present early in life with amenorrhea, elevated gonadotropins, and normal karyotypes.