A Randomized Controlled Trial of Ovarian Suppression in Premenopausal Women: No Change in Free-Living Energy Expenditure.

OBJECTIVE: The purpose of this study was to determine whether suppression of ovarian function (gonadotropin-releasing hormone agonist [GnRHAG ]) for 24 weeks in premenopausal women approaching menopause causes changes in body composition and a decline in free-living physical activity energy expenditure (PAEE) and whether endurance exercise training attenuates the changes. METHODS: Premenopausal women who were approaching menopause (mean [SD]: age 46 [3] years, BMI 26.3 [4.8] kg/m2 ) were randomized to 24 weeks of GnRHAG (n = 14), GnRHAG + Exercise (n = 11), or placebo (n = 9). Endurance exercise was performed 4 days per week with the goal of expending 200 to 300 kcal per session. Primary outcome measurements included body composition by dual-energy x-ray absorptiometry, total daily energy expenditure (TDEE), and PAEE by doubly labeled water, and resting energy expenditure (REE) by indirect calorimetry. RESULTS: Changes in TDEE, PAEE, REE, or body composition were not different between groups. However, within the GnRHAG group, fat mass increased (mean [SE]: total 1.7 [0.4] kg, trunk 0.9 [0.2] kg, leg 0.6 [0.2] kg) and fat-free leg mass decreased (mean [SE]: -0.4 [0.2] kg) significantly. CONCLUSIONS: In premenopausal women approaching menopause, ovarian hormone suppression resulted in increased adiposity without alterations in TDEE, PAEE, or REE.

Assessment of ovarian function after chemotherapy in women with early and locally advanced breast cancer from Serbia.

PURPOSE: Among harmful effects of chemotherapy is the reduction of ovarian function. The aim was to determine the serum levels of FSH, LH, estradiol and AMH after chemotherapy followed by endocrine therapy in breast cancer patients. METHODS: The study included 40 premenopausal hormone receptor-positive breast cancer patients aged 33-50 years. Anthracycline-based chemotherapy received 14/40 while anthracycline-taxane combination received 26/40 of patients, followed by tamoxifen (30/40) or tamoxifen plus goserelin (10/40). All of them experienced chemotherapy-induced secondary amenorrhea. Hormone levels were determined by ELISA. Statistics included Spearman's test, Mann-Whitney test and multiple linear regression analysis. RESULTS: Undetectable AMH levels were observed in 62.5 and 33.3% of patients with time period < 2 and ≥ 2 years from completion of chemotherapy to sample collection. Median levels of hormones for patients treated with anthracycline-based compared to anthracycline-taxane therapy were: 15.5 vs. 22.3 IU/L for FSH; 10.9 vs. 13.6 IU/L for LH; 55.5 vs. 39.5 pg/mL for estradiol; 0.11 vs. 0.11 ng/mL for AMH. The multiple linear regression showed that: women who received goserelin had significantly lower FSH; those with shorter time from completion of chemotherapy to sample collection had significantly higher LH and lower estradiol; younger women had higher AMH levels. CONCLUSIONS: The ovarian function was recovered from chemotherapy-induced secondary amenorrhea with time elapsed since the completion of adjuvant chemotherapy. It may be less disrupted in patients who received anthracycline-based chemotherapy and goserelin plus tamoxifen, as well.

Accuracy and safety verification of ovarian reserve assessment technique for ovarian tissue transplantation using optical coherence tomography in mice ovary.

Except for histological study, there are currently no suitable techniques available for the detection and identification of primordial follicles in ovary of primary ovarian insufficiency patients who have undetectable AMH levels. Also, the ability to locate and quantify follicles on ovarian cortex strips, without fixation, is valuable for patients who could undergo subsequent successful ovarian tissue transplantation. Although optical coherence tomography (OCT) is a well-established high resolution imaging technique without fixation commonly applied in biomedicine, few reports are available on ovarian tissue imaging. In present study, we established standard OCT follicle images at each developmental stage, including the primordial follicle, and demonstrated the efficacy of OCT to estimate IVF outcome in transplanted mice ovary like ovarian reserve tests. Unfortunately, the current commercial OCT could not be used to accurate follicle count the number of follicles for whole ovary, because the maximum depth of examination was 100 µm. And we demonstrated the safety of OCT examination, it did not affect IVF outcome and birth defect rate, and reproductive ability. Although there is room for improvement, these findings will be first step to bring OCT examination a step closer to clinical application for measuring true ovarian reserve and localizing follicles.

No. 341-Diagnosis and Management of Adnexal Torsion in Children, Adolescents, and Adults.

OBJECTIVE: To review the evidence and provide recommendations on the diagnosis and management of adnexal torsion in children, adolescents, and women. OUTCOMES: Elements evaluated include the risk factors, diagnostic accuracy, management options, and outcomes of adnexal torsion. EVIDENCE: Published literature was retrieved through searches of MEDLINE, Embase, CINAHL, and the Cochrane Library using appropriate controlled vocabulary and key words ("adnexal torsion," "ovarian torsion"). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and new material incorporated in the guideline to December 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The evidence obtained was reviewed and evaluated by the Canadian Paediatric and Adolescent Gynaecology and Obstetrics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors. Recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS AND COSTS: Guideline implementation should assist the practitioner in developing an optimal approach to the diagnosis and management of adnexal torsion while minimizing harm and improving patient outcomes. VALIDATION: These guidelines have been reviewed and approved by the Gynaecology Committee of the SOGC and approved by the council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada SUMMARY STATEMENTS: RECOMMENDATIONS.

Anti-Müllerian hormone and assessment of ovarian reserve after ovarian toxic treatment: a systematic narrative review.

Since serum anti-Müllerian hormone (AMH) levels enable quantitative evaluation of ovarian damage, we conducted a computer-based search, using key words, of all articles published in English through the PubMed database from inception until September 2013 to summarize available studies evaluating ovarian reserve after ovarian toxic interventions to discuss the usefulness of serum AMH levels. We found that most of the studies demonstrated a decline in serum AMH levels when compared to control or pretreatment levels, with levels dependent on the type of treatment modality. Measurement of serum AMH levels enables quantitative evaluation of ovarian damage caused by ovarian toxic interventions, such as chemotherapy and radiotherapy, instead of qualitative evaluation using menstrual condition or basal follicle-stimulating hormone levels. Serum AMH levels are becoming indispensable to assess the ovarian reserve of patients who desire preservation of ovarian function for fertility and endogenous sex steroid hormones.

Ovarian reserve assessment in women with different stages of pelvic endometriosis.

INTRODUCTION: Endometriosis is defined as the appearance of ectopic endometrial cells outside the uterine cavity. Ectopic cells demonstrate functional similarity to eutopic cells, but structural and molecular differences are significant and manifest themselves in gene expression of the metalloproteinase genes, integrin or the Bcl-2 gene. Pelvic pain remains to be the main symptom of the disease. Endometriosis may cause dysfunction of the reproductive system and lead to infertility. Pathogenesis of infertility in endometriosis is based on its influence on the hormonal, biochemical and immunological changes in the eutopic endometrium, as well as structural damages of the ovaries and the fallopian tubes. OBJECTIVES: The aim of the study was to assess the ovarian reserve in patients with endometriosis. MATERIAL AND METHODS: A total of 39 patients (aged 22-34 years) with different stages of endometrial changes were recruited for the study. The number of antral follicles was rated by vaginal ultrasonography and the level of FSH was measured between days 1-3 of the menstrual cycle. The stage of the disease was established after laparoscopy with the rASRM scale. RESULTS: No statistically significant correlation between the number of follicles (AFC), the level of FSH and the stage of endometriosis was found. CONCLUSIONS: Evaluation of the number of antral follicles and measurements of the FSH level do not allow to predict the ovarian reserve in women with endometriosis.

[Assessment of ovarian reserve with anti-Müllerian hormone in female patients with systemic lupus erythematosus].

OBJECTIVE: To evaluate the serum level of anti-Müllerian hormone (AMH) in female patients with systemic lupus erythematosus (SLE) and identify its correlations with age and cyclophosphamide (CYC) therapy. METHODS: A total of 77 SLE female patients and 38 control healthy women with regular menstrual cycles were recruited. AMH was measured by enzyme linked immunosorbent assay (ELISA) kit. Follicle-stimulating hormone (FSH), estradiol (E2) and antral follicle count (AFC) of bilateral ovary were detected at the third day of menstrual cycle. RESULTS: Their mean age was (29 ± 5) years (range, 20-40) and the mean duration (2.7 ± 2.4) years. The mean serum level of AMH was (1.5 ± 1.3) µg/L and AFC 10 ± 7. Linear regression revealed AFC (r = 0.9, P < 0.01) was associated with the level of AMH. The mean levels of AMH and AFC were significantly higher in patients naїve to CYC therapy than in those under exposure, but lower than that in healthy control (P < 0.01). No difference existed in FSH and E2 among 3 groups. Compared with those above 30 years old, the patients aged 30 years and younger had significantly higher level of AMH (P < 0.01). The Spearman's correlation analysis indicated that each 5 gm of CYC exposure were independently associated with a lower level of AMH (r = -0.4, P < 0.01). CONCLUSION: As a more sensitive marker of ovarian reserve, AMH is associated with age and the cumulative dose of CYC. SLE patients aged >30 years and under exposure to CYC >10 g should be closely monitored for potential adverse events.

Racial and ethnic differences in the physiology and clinical symptoms of menopause.

More than 4 million menopausal women are from ethnic minority groups. Over the past 25 years, recognition of the importance of social, emotional, and physical changes of midlife to women's long-term health and well-being has emerged. Multiple factors influence how a woman perceives menopausal changes and what she addresses as associated symptoms. Factors such as educational level to socioeconomic status, health-related factors, stress, and marital status influence these choices. Increasingly, researchers are reporting on the impact of race and ethnicity on menopausal symptoms. Understanding similarities and differences among women's perceptions, attitudes, and expectations surrounding menopause improves delivery of culturally appropriate care and promotes lifestyles that may decrease symptoms and increase quality of life. Historically, the majority of the research in this area has been conducted in Western countries with clinical samples of women predominantly from European backgrounds. Thus, this population has shaped the emerging clinical picture of the midlife menopausal transition. Recently, studies of non-European women, both in the United States and internationally, indicate significant variations in their experiences during this transition, but these cultural differences have not broadened the understanding of the meaning of this universal experience. To date, there are still large knowledge gaps in race, ethnic, and cultural differences in menopausal health. The content of this review summarizes the current body of knowledge on racial differences in the menopause experience.

Antimüllerian hormone, the assessment of the ovarian reserve, and the reproductive outcome of the young patient with cancer.

The accurate assessment of the ovarian reserve has long been a key goal in reproductive medicine. The recognition that serum antimüllerian hormone provides an indirect measure of the ovarian reserve has led to its rapid adoption in assisted conception, and wide exploration of its potential across the reproductive lifespan from the neonate to the menopause. In this short review we discuss its relationship with the ovarian reserve in its varied meanings, and in various contexts. These include in childhood and adolescence, and in the assessment of the impact of cancer therapy on the female reproductive tract. These therapies can adversely impact all aspects of female reproduction, including hypothalamic, pituitary, and ovarian hormonal activity, and the ability of the uterus to support a successful pregnancy.

An assessment of female university students' attitudes toward screening technologies for ovarian reserve.

OBJECTIVE: To assess female university students' attitudes toward screening technologies for ovarian reserve and their potential influence on career and family planning decisions. DESIGN: Online survey. SETTING: Not applicable. PATIENT(S): Respondents from 4 universities in Northern California. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Proportion with interest in screening technologies for ovarian reserve. RESULT(S): Of the 328 respondents, 79% were interested in learning about the current status of their ovarian reserve. Hypothetically, if informed that ovarian reserve was very low, 53% would consider oocyte cryopreservation (even when informed that it is experimental); however, only 29% would consider stopping educational or professional pursuits to focus on conceiving. Participants also demonstrated gaps in knowledge, believing that the decline in ovarian reserve starts later than it actually does, that diet and nutrition can preserve ovarian reserve, and that infertility treatments are highly effective regardless of how severe the depletion of the egg supply is. CONCLUSION(S): Women attending universities are interested in assessing their own ovarian reserve. Gaps in knowledge about ovarian reserve exist among these reproductive-aged women.

Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone.

BACKGROUND: The aim was to assess possible treatment-induced gonadal damage in a cohort of adult female childhood cancer survivors (CCS) using anti-Müllerian hormone (AMH), the most sensitive marker of ovarian reserve. METHODS: A total cohort of 185 survivors was compared with 42 control subjects. The median follow-up time was 18.1 years (range 4.1-43.2 year). RESULTS: Median AMH concentrations in the analysed cohort were not different from controls (median 1.7 versus 2.1 microg/l; P = 0.57). However, AMH levels were lower than the 10th percentile of normal values in 27% (49/182) of our survivors. In addition, 43% (79/182) had AMH levels lower than 1.4 microg/l, a previously established cut-off value which predicts ongoing pregnancy after assisted reproduction. There were no differences in AMH levels in subgroups classified according to disease. However, survivors treated with three or more procarbazine containing chemotherapy cycles had significantly lower AMH levels than controls (median 0.5 microg/l; P = 0.004). Also survivors treated with abdominal or total body irradiation had significantly lower AMH levels than controls (median < 0.1 microg/l; P < 0.001). CONCLUSIONS: AMH can be used to identify subgroups of CCS at risk for decreased fertility or premature ovarian failure. In these survivors, options for fertility preservation should be considered prior to starting treatment since they may be at risk for poor chances of pregnancy after assisted reproductive treatment.

The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report.

OBJECTIVE: To review all available data and recommend a definition for polycystic ovary syndrome (PCOS) based on published peer-reviewed data, whether already in use or not, to guide clinical diagnosis and future research. DESIGN: Literature review and expert consensus. SETTING: Professional society. PATIENTS: None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. RESULT(S): The Task Force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the Androgen Excess and PCOS (AE-PCOS) Society AE-PCOS Board of Directors. No section was finalized until all members were satisfied with the contents, and minority opinions noted. Statements were not included that were not supported by peer-reviewed evidence. CONCLUSION(S): Based on the available data, it is the view of the AE-PCOS Society Task Force that PCOS should be defined by the presence of hyperandrogenism (clinical and/or biochemical), ovarian dysfunction (oligo-anovulation and/or polycystic ovaries), and the exclusion of related disorders. However, a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism, but recognized that more data are required before validating this supposition. Finally, the Task Force recognized and fully expects that the definition of this syndrome will evolve over time to incorporate new research findings.

Assessment of pituitary and steroid hormones and members of the TGF-beta superfamily for ovarian function in patients with congenital uterus and vaginal aplasia (MRKH syndrome).

Patients with Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome have congenital uterine and vaginal aplasia. The main question of this study was, if the absence of a uterus along with other genital and organ malformations could contribute to hormone or other growth factor protein fluctuations involved in communication between the hypothalamus-pituitary axis, ovaries and uterus. Serum from 56 MRKH patients (mean 27.6 years) and 22 female controls (mean 30.7 years) were analyzed using ELISA to determine levels of pituitary and steroid hormones (LH, FSH, estradiol, progesterone), growth factors of the TGF-beta superfamily like activin A, inhibin B, and anti-Müllerian hormone (AMH). All serum levels were analyzed in relation to other organ malformations. Compared to controls, all 56 patients, including 5% with streak ovaries or unilateral ovarian aplasia, were generally similar in hormone and growth factor levels and could be grouped into hormonal phases. However, compared to controls LH/FSH and FSH/LH ratios of patients had significantly higher and lower mean values, of 2.75-fold (p=0.015) and 1.9-fold (p=0.002), respectively. Undetectable inhibin B levels of<10 pg/ml (p=0.05) were noted in 41.1% of MRKH patients, resulting in significantly higher activin A/inhibin B ratios (p<0.001). MRKH patients have hormonal phases supporting ovarian function, but patients with low FSH/LH ratios and undetectable inhibin B levels (<10 pg/ml) could represent cycle phasing irregularities. A model is discussed regarding our findings and the loss of ovarian-uterine communication.

Stress, depression, and coronary artery disease: modeling comorbidity in female primates.

Depression and coronary heart disease (CHD) are leading contributors to disease burden in women. CHD and depression are comorbid; whether they have common etiology or depression causes CHD is unclear. The underlying pathology of CHD, coronary artery atherosclerosis (CAA), is present decades before CHD, and the temporal relationship between depression and CAA is unclear. The evidence of involvement of depression in early CAA in cynomolgus monkeys, an established model of CAA and depression, is summarized. Like people, monkeys may respond to the stress of low social status with depressive behavior accompanied by perturbations in hypothalamic-pituitary-adrenal (HPA), autonomic nervous system, lipid metabolism, ovarian, and neural serotonergic system function, all of which are associated with exacerbated CAA. The primate data are consistent with the hypothesis that depression may cause CAA, and also with the hypothesis that CAA and depression may be the result of social stress. More study is needed to discriminate between these two possibilities. The primate data paint a compelling picture of depression as a whole-body disease.

Management of reproductive needs in cancer patients: clinical perspectives.

Over the last few decades, a growing number of cancer survivors cured or in long-term remission following successful cancer treatment, have particular reproductive health needs. Achieving or preventing pregnancies, as well as replacement of sex hormone deficiency are three main reproductive issues. Managing such reproductive needs requires a close collaboration between specialists in oncology, reproductive endocrinology and andrology. Currently, there are few collaborative efforts to bridge the gaps between these three subspecialties. Patients are often lost between oncologists who lack the interest in addressing reproductive issues, and reproductive endocrinologists and andrologists, who do not have the clinical practice model to provide emergency consultations for cancer patients or adequate follow-up. On the other hand, there is severe deficiency in patients' education and knowledge regarding the consequences of cancer treatment on their reproductive life and the available modern technologies in reproductive medicine. Perhaps the time has come to build a new medical subspecialty that can address and manage the long-term health needs of cancer survivors, including reproductive needs.

Homeostasis model assessment-insulin resistance (HOMA-IR), a key role for assessing the ovulation function in polycystic ovary syndrome (PCOS) patients with insulin resistance.

According to our research, we evaluated that for the ovulation function in polycystic ovary syndrome (PCOS) with IR, Homeostasis model assessment-insulin resistance (HOMA-IR) is a clinic , simple and practical and sensitive Index for assessing the ovualtion failure. Meanwhile, after anti-IR treatment, HOMA-IR is also a reliable and simple for accessing the recoverying ovulation function.

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.