Low anti-Müllerian Hormone Research Articles

Usefulness of the Ultrasensitive Anti-Müllerian Hormone Assay for Predicting True Ovarian Reserve.

Serum concentration of anti-Müllerian hormone (AMH) is a useful marker for ovarian reserve. Measurement of AMH in clinical practice has gained widespread use to predict parameters such as the ovarian response, menopause, and recovery after chemotherapy. However, undetectable AMH levels assayed by conventional enzyme-linked immunosorbent assay (ELISA) kits fail to predict depletion of follicles because of low sensitivity of the kits. We investigated whether a recently developed ultrasensitive ELISA kit, picoAMH, would be more effective at detecting very low AMH levels in association with menstrual status. We analyzed 68 women with undetectable serum AMH levels using an ELISA kit, AMH Gen II. The AMH concentration of the same samples was detected in 36 samples using picoAMH; 32 samples were within the standard range, and 4 samples were out of the standard range but still detectable. Thirty-two women whose AMH levels were undetectable using the picoAMH all showed amenorrhea. We also found a significant correlation between the classes of serum AMH levels (undetectable, detectable under the limit of quantification, and measurable within the assay range) and menstrual status. Five of the 6 amenorrheic women with detectable AMH eventually achieved follicle growth. The present study demonstrated that very low AMH levels detectable using picoAMH correspond well to current and future ovulation status. This suggests that serum AMH levels can be useful for the assessment of ovarian reserve and follow-up of women with a declined ovarian reserve.

Antimüllerian hormone in relation to tobacco and marijuana use and sources of indoor heating/cooking

To evaluate exposure to tobacco, marijuana, and indoor heating/cooking sources in relation to antimüllerian hormone (AMH) levels. Cross-sectional analysis in a sample of premenopausal women (n = 913) enrolled in the Sister Study cohort (n = 50,884). Not applicable. Women, ages 35-54 years at time of enrollment, with an archived serum sample and at least one intact ovary and classified as premenopausal. Not applicable. Serum AMH (ng/mL) levels ascertained by ultrasensitive ELISA assay. Lower AMH levels were associated with sources of indoor heating, including burning wood (-36.0%; 95% confidence interval [CI], -55.7%, -7.8%) or artificial fire logs (-45.8%; 95% CI, -67.2%, -10.4%) at least 10 times/year in a residential indoor stove/fireplace. Lower AMH levels were also observed in women who were current smokers of ≥20 cigarettes/day relative to nonsmokers (-56.2%; 95% CI, -80.3%, -2.8%) and in women with 10+ years of adult environmental tobacco smoke (ETS) exposure (-31.3%; 95% CI, -51.3%, -3.1%), but no associations were observed for marijuana use. We confirmed previously reported findings of lower AMH levels in current heavy smokers and also found associations for long-term ETS exposure and indoor burning of wood or artificial fire logs. These findings suggest that combustion by-products from common exposures can have toxic effects on the human ovary.

Self-collected dried blood spots as a tool for measuring ovarian reserve in young female cancer survivors.

Are female young cancer survivors (YCS) able to self-collect high-quality dried blood spots (DBSs) at home to provide biospecimens for studying ovarian reserve? YCS can self-collect high-quality DBS specimens in non-clinical settings, and anti-Mullerian hormone (AMH) levels can be assayed in such specimens. Large-scale biosample collection is a barrier to studying ovarian reserve in YCS. DBS collected by research personnel has high acceptability. AMH levels measured in DBS are highly correlated with those measured by serum-based methods. In a prospective cohort study, YCS were recruited to self-collect DBS samples. AMH levels were assayed in 112 samples. YCS participants, ages 18-44, were recruited from a nationwide longitudinal cohort and DBS collection materials were posted to them. AMH levels were assayed by the Ansh DBS AMH ELISA and compared according to participant characteristics. Among 163 potential participants, 123 (75%) were enrolled. Of those enrolled, 112 (91%) were able to complete DBS self-collection and submit mailed samples adequate for measuring AMH. Participants (mean age 31.6 [SD 5.5]) were 85% white, 87% college graduates and 46% reported higher income. Common cancer types were lymphoma and leukemia (34%), breast cancer (30%) and thyroid or skin cancer (8%). The geometric mean (95% confidence interval) AMH level in DBS samples was 0.24 ng/ml (0.16-0.36). In adjusted analysis, AMH levels for survivors of breast cancer (0.02 ng/ml [0.01-0.07]) or leukemia/lymphoma (0.03 ng/ml [0.01-0.08]) were lower than the levels in thyroid or skin cancer survivors (0.12 ng/ml [0.03-0.44]). Pelvic radiation remained associated with lower AMH levels (0.20 ng/ml [0.10-0.40] in unexposed versus 0.02 ng/ml [0.01-0.06] in exposed). Amenorrheic survivors had AMH levels (0.02 ng/ml [0.01-0.06]) that were lower than those of YCS with 7-9 (0.09 ng/ml [0.03-0.32]) or ≥10 (0.17 ng/ml [0.08-0.37]) menstrual periods in the past year. The results are generalizable to a population of highly educated, higher income YCS. It is unclear how generalizable the results are to other populations. Self-collected DBS is a patient-friendly and minimally invasive tool for studying ovarian reserve in geographically diverse populations. Research related to the development of this paper was supported by the National Institutes of Health, grants UL1 RR024926 pilot and HD080952-02, and by the American Cancer Society MRSG-08-110-01-CCE. The authors report no competing interests.

The Role of Anti-Müllerian Hormone in the Characterization of the Different Polycystic Ovary Syndrome Phenotypes.

Rotterdam criteria identified 4 polycystic ovary syndrome (PCOS) phenotypes based on the combination of anovulation (ANOV), hyperandrogenism (HA), and polycystic ovaries (PCOs): phenotype 1 (ANOV + HA + PCO), phenotype 2 (ANOV + HA), phenotype 3 (HA + PCO), and phenotype 4 (ANOV + PCO). Anti-Müllerian hormone (AMH) was suggested to play a pathophysiologic and diagnostic role in this syndrome. The aim of this study was to compare AMH levels among the different phenotypes in relation to clinical, endocrine, and metabolic features. We enrolled 117 women with PCOS (body mass index: 25.89 ± 6.20 kg/m(2), age range: 18-37 years) and 24 controls. Anthropometric characteristics, hirsutism score, ultrasound ovarian features, and hormonal parameters, including AMH, were evaluated. Each participant also underwent an oral glucose tolerance test and an euglycemic-hyperinsulinemic clamp. The prevalence of phenotypes 1 to 4 was 62.4%, 8.6%, 11.1%, and 17.9%, respectively. Body mass index and insulin resistance indexes were similar among the groups. Phenotype 1 showed the highest luteinizing hormone, androgens levels, ovarian volume, and AMH concentrations (9.27 ± 8.17 ng/mL,P< .05) versus phenotype 2 and controls. Phenotype 2 women were hirsute, showed an intermediate free androgen index value, low ovarian volume, and low AMH levels (4.05 ± 4.12 ng/mL). Phenotype 3 showed an intermediate state of HA and slightly augmented AMH levels (5.87 ± 4.35 ng/mL). The clinical and endocrine characteristics of phenotype 4 resembled those of controls, except for higher ovarian volume and AMH levels (7.62 ± 3.85 ng/mL;P< .05). Our results highlight the heterogeneity of the association between increased AMH levels, menstrual dysfunction, and HA in the different PCOS phenotypes, thus offering a key to an understanding of the current controversy on the value of AMH measurement in PCOS.

Anti-Müllerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations.

STUDY QUESTIONDo women with BRCA1 or BRCA2 mutations have reduced ovarian reserve, as measured by circulating anti-Müllerian hormone (AMH) concentration?SUMMARY ANSWERWomen with a germline mutation in BRCA1 have reduced ovarian reserve as measured by AMH.WHAT IS KNOWN ALREADYThe DNA repair enzymes encoded by BRCA1 and BRCA2 are implicated in reproductive aging. Circulating AMH is a biomarker of ovarian reserve and hence reproductive lifespan.STUDY DESIGN, SIZE, DURATIONThis was a cross-sectional study of AMH concentrations of 693 women at the time of enrolment into the Kathleen Cuningham Foundation Consortium for research in the Familial Breast Cancer (kConFab) cohort study (recruitment from 19 August 1997 until 18 September 2012). AMH was measured on stored plasma samples between November 2014 and January 2015 using an electrochemiluminescence immunoassay platform.PARTICIPANTS/MATERIALS, SETTING, METHODSEligible women were from families segregating BRCA1 or BRCA2 mutations and had known mutation status. Participants were aged 25–45 years, had no personal history of cancer, retained both ovaries and were not pregnant or breastfeeding at the time of plasma storage. Circulating AMH was measured for 172 carriers and 216 non-carriers from families carrying BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying BRCA2 mutations. Associations between plasma AMH concentration and carrier status were tested by linear regression, adjusted for age at plasma storage, oral contraceptive use, body mass index and cigarette smoking.MAIN RESULTS AND THE ROLE OF CHANCEMean AMH concentration was negatively associated with age (P < 0.001). Mutation carriers were younger at blood draw than non-carriers (P ≤ 0.031). BRCA1 mutation carriers had, on average, 25% (95% CI: 5%–41%, P = 0.02) lower AMH concentrations than non-carriers and were more likely to have AMH concentrations in the lowest quartile for age (OR 1.84, 95% CI: 1.11–303, P = 0.02). There was no evidence of an association between AMH concentration and BRCA2 mutation status (P = 0.94).LIMITATIONS, REASONS FOR CAUTIONAMH does not directly measure the primordial follicle pool. The clinical implications of the lower AMH concentrations seen in BRCA1 mutation carriers cannot be assessed by this study design.WIDER IMPLICATIONS OF THE FINDINGSWomen with a germline mutation in BRCA1 may have reduced ovarian reserve. This is consistent with other smaller studies in the literature and has potential implications for fertility and reproductive lifespan.STUDY FUNDING/COMPETING INTEREST(S)kConFab is supported by a grant from the Australian National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. K.A.P. is an Australian National Breast Cancer Foundation Practitioner Fellow. J.L.H. is a NHMRC Senior Principal Research Fellow. M.H. is a NHMRC Practitioner Fellow. R.A.A. reports personal fees from Roche Diagnostics & Beckman Coulter outside the submitted work and C.S. reports other earnings from Melbourne IVF outside the submitted work. The remaining authors have nothing to declare and no conflicts of interest.

Effect of sleeve gastrectomy bariatric surgery-induced weight loss on serum AMH levels in reproductive aged women

Objective: This study aims to evaluate the change in serum anti-Mullerian hormone (AMH) levels in patients with morbid obesity undergoing bariatric surgery for weight loss.Material and methods: In this prospective observational study, 75 patients of reproductive age (20–35 years) undergoing bariatric surgery for morbid obesity were followed up after six months to determine the changes in weight, Body Mass Index (BMI), menstrual pattern and serum AMH. The results were further studied on basis of pre operative classification of patients in polycystic ovary syndrome (PCOS) and non-PCOS group.Result: The serum AMH levels were statistically higher in patients of PCOS group pre operatively and at the end of six months in comparison to non-PCOS patients. The AMH values reduced post operatively in both groups significantly so much in the values though not significant statistically. Non-PCOS patients had lower AMH values pre operatively and showed a trend towards reducing ovarian reserve after six months. The overall change in AMH values in both groups was statistically significant as was the normalization of menstrual irregularity.Conclusion: Morbidly obese patients with PCOS appear to benefit from bariatric surgery both in terms of regularization of menstrual function and normalization of serum AMH values.

Serum inhibin B values in infertile patients

The increased interest in inhibin B generated by Sertoli cells is due to the fact that on the basis of findings, some authors recorded a relationship between the level of this hormone and infertility. The paper gives the results of an investigation of male sex hormones (inhibin B, follicle-stimulating and anti-Mullerian hormones) in the serum of patients with azoospermia (Group 1), who had spermatogenesis, as evidenced by testicular biopsy, who had no spermatogenesis (Group 2), and who had oligoasthenozoospermia (Group 3). The investigation indicated that Group 1 had a normal inhibin B level that was more than twice lower in Group 2. In addition, the latter group was recorded to have elevated follicle-stimulating hormone levels and low anti-Mullerian hormone concentrations as compared to Group 1.

Effect of salpingectomy, ovarian cystectomy and unilateral salpingo-oopherectomy on ovarian reserve

Pelvic surgery can affect ovarian reserve, but estimates of the potential effect of different surgical procedures are lacking. This study examines the markers of ovarian reserve after different procedures in order to help the provision of informed consent before surgery. Anti-Müllerian hormone (AMH), antral follicle count (AFC) and follicle-stimulating hormone (FSH) of women with a history of salpingectomy, ovarian cystectomy or unilateral salpingo-oophorectomy were compared to those without history of surgery using cross-sectional data adjusting for patient and clinical factors in multivariable regression model. There were 138 women who had had salpingectomy, 36 unilateral salpingo-oopherectomy, 41 cystectomy for ovarian cysts that are other than endometrioma and 40 women had had excision of endometrioma. There was no significant difference in AMH (9 %; p = 0.33), AFC (−2 %; p = 0.59) or FSH (−14 %; p = 0.21) in women with a history of salpingectomy compared to women without surgery. Women with a history of unilateral salpingo-oophorectomy were found to have significantly lower AMH (−54 %; p = 0.001). These women also had lower AFC (−28 %; p = 0.34) and higher FSH (14 %; p = 0.06), the effect of which did not reach statistical significance. The study did not find any significant associations between a history of cystectomy, for disease other than endometrioma and AMH (7 %; p = 0.62), AFC (13 %; p = 0.18) or FSH. (11 %; p = 0.16). Women with a history of cystectomy for ovarian endometrioma had 66 % lower AMH (p = 0.002). Surgery for endometrioma did not significantly affect AFC (14 %; p = 0.22) or FSH (10 %; p = 0.28). Salpingo-oopherectomy and cystectomy for endometrioma cause a significant reduction in AMH levels. Neither salpingectomy nor cystectomy for cysts other than endometrioma has appreciable effects on ovarian reserve.Electronic supplementary materialThe online version of this article (doi:10.1007/s10397-016-0940-x) contains supplementary material, which is available to authorized users.

Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies.

The purpose of this study is to investigate if female patients with lymphoma demonstrate diminished ovarian reserve prior to initiation of the lymphoma treatment. Sixty-four patients with newly diagnosed lymphoma undergoing controlled ovarian hyperstimulation for fertility preservation were compared with 365 healthy controls undergoing elective oocyte cryopreservation (controlled ovarian hyperstimulation (COH)) and 128 patients with other types of malignancy prompting fertility preservation. The data of all lymphoma patients, all elective, and all the patients with other types of malignancy who met the inclusion criteria and underwent COH for fertility preservation during the study period were retrospectively analyzed. Primary outcomes included serum anti-Müllerian hormone (AMH) levels (ng/mL) and antral follicle count (AFC). Patients in the lymphoma group demonstrated significantly lower AMH levels and AFC and had less oocytes harvested and cryopreserved when compared to healthy controls as well as patients with other malignancies. Patients with lymphoma demonstrate diminished ovarian reserve when compared with healthy controls and patients with other malignancies. This should be taken into consideration when deciding on the dose for COH.

Effects of cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome of in vitro fertilization-embryo transfer cycle

To investigate the impact of previous cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Totally 622 infertility patients were retrospectively investigated who underwent first IVF/ICSI-ET cycle in Reproductive Hospital Affiliated to Shandong University from January 2013 to June 2014. There were 153 cases who had been removed ovarian cyst by cystectomy surgeries recruited as study group, in which 44 cases of ovarian endometriosis cyst, 35 cases of benign ovarian teratomas, 67 cases of simple ovarian cyst and 7 cases of ovarian mucinous cystadenoma. In contrast, 469 infertility patients with tubal-factor infertility or male factor were included as control group. The age-matched women in the control group had no ovarian surgery previously. The indicators of ovarian reserve and pregnancy outcome were analyzed between two groups. The influence of different types of ovarian cysts on ovarian reserve and pregnancy outcome in IVF/ICSI-ET cycles were also studied, ovarian endometriosis cyst was studied as Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst and mucinous cystadenoma. (1) The significantly lower serum antimullerian hormone (AMH) level (median: 1.92 versus 2.90 mg/L), antral follicle count (AFC; median: 12.0 versus 13.0), retrieved oocytes (12±5 versus 13±6) and the number of embryo cryopreserved (median: 1.0 versus 3.0) were found in study group compared with control group (all P<0.05). There was no statistical difference between two group for the following parameters, such as basal FSH level, the total dosage of gonadotropin duration and the total dosage of gonadotropin (all P>0.05). A better clinical pregnancy rate was achieved in control group (61.6%, 241/391) than that in study group (61.4%, 81/132), but no significant difference was existed (P=0.96). (2) Compared to Group B, Group A had fewer AFC, lower serum AMH level, retrieved oocytes and the number of embryo cryopreserved (11±4 versus 13±5; 1.65 versus 2.15 mg/L; 9±4 versus 13±5; 0 versus 2.0; all P< 0.01). There was a lower clinical pregnancy rate in Group A than that in Group B [50.0% (19/38) versus 66.0% (62/94)], accompanying with higher abortion rate [3/19 versus 9.7% (6/62)], but no differences were observed (all P>0.05). Ovarian reserve declines after the cystectomy for ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI-ET cycle, resulting in a decrease of the number of retrieved oocytes and the number of embryo cryopreserved, but do not influence clinical pregnancy outcome. Ovarian reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst than other ovarian benign cyst.

Low Anti-Müllerian Hormone in Pediatric Cancer Survivors in the Early Years after Gonadotoxic Therapy

Study ObjectiveTo obtain anti-Müllerian hormone (AMH) levels in female childhood cancer survivors and determine the association of therapeutic exposures with diminished ovarian reserve (DOR). DesignCross-sectional study. SettingAcademic medical center. ParticipantsForty-nine survivors (mean age = 14.9 years, SD = 3.3 years; mean time without therapy = 7.5 years, SD = 3.6 years) who received alkylator/heavy metal chemotherapy, and/or radiation exposure to the ovaries with 2 or more years without therapy were recruited. InterventionsNone. Main Outcome MeasuresAMH, follicle stimulating hormone (FSH) levels (random), and therapeutic characteristics such as cyclophosphamide equivalent dose (CED), heavy metal exposure, and bilateral ovarian radiation exposure were determined for each subject. DOR was defined as a low AMH (less than the fifth percentile for age-matched controls), and premature ovarian insufficiency as an FSH greater than 40 IU/L with AMH less than the fifth percentile. ResultsFourteen subjects (28.6%) had DOR, and 5 (10.2%) had premature ovarian insufficiency. Those with a low AMH were more likely exposed to a higher CED (P = .001) and/or bilateral ovarian radiation exposure (P = .048). In the multivariate model of DOR adjusted for age at diagnosis, DOR was associated with bilateral radiation (odds ratio = 39.9; 95% confidence interval 2.1-759.7; P = .04). There was a nonsignificant trend with increasing odds of low AMH with increased CED. ConclusionDOR, defined by an AMH less than the fifth percentile, was observed in more than one-quarter of pediatric cancer survivors exposed to gonadotoxic cancer therapy and was significantly associated with bilateral ovarian irradiation. Identifying risk factors for low AMH prompts AMH and FSH surveillance in the early years after cancer therapy and, if needed, early referral to a reproductive specialist.

IVF results in patients with very low serum AMH are significantly affected by chronological age.

The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-müllerian hormone (AMH) and to investigate factors affecting their probability of pregnancy. The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5ng/ml was retrospectively analyzed. Cycle cancellation rate was 14.5%; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35-39 or 40-43 (31% vs. 23.2% vs. 10.2%, respectively; p = 0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14-0.49ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level. Women with very low (<0.5ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF.

Ovarian Reserve Assessment in Users of Oral Contraception Seeking Fertility Advice on their Reproductive Lifespan

STUDY QUESTION: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced? SUMMARY ANSWER: Ovarian reserve parameters defined by anti-Mullerian hormone (AMH) antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%) 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users. WHAT IS KNOWN ALREADY: AMH and AFC have proved to be reliable predictors of ovarian ageing. In women AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain. STUDY DESIGN SIZE DURATION: A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users. PARTICIPANTS/MATERIALS SETTING METHODS: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC ovarian volume pathology) a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women 244 (27.5%) used OC. In a linear regression analyses adjusted for age ovarian volume was 50% lower (95% CI 45.1-53.7%) AMH was 19% lower (95% CI 9.1-29.3%) and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6 95% CI 1.1; 2.4 P = 0.03). Furthermore we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age BMI smoking and maternal age at menopause. LIMITATIONS REASON FOR CAUTION: The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC. WIDER IMPLICATIONS OF THE FINDINGS: OC has a major impact on the ovarian volume and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan. STUDY FUNDING/COMPETING INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests. TRIAL REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081). (c) The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions please email: journals.permissions@oup.com.

Relevance of endoglin, IL-1α, IL-1β and anti-ovarian antibodies in females with multiple sclerosis

Few studies support the concept of reduced fertility in females with multiple sclerosis (MS). Recently we reported on reduced serum levels of Anti-Müllerian Hormone (AMH) in reproductive-age females with MS, suggestive of reduced ovarian reserve. The cause for this observation is not evident and remains speculative. The aim of the study is to examine possible immunological mechanisms interfering with fertility, as well as ovarian reserve that might affect the reproductive potential in women with MS.ELISA experiments were done to detect anti-ovarian antibodies (AOA), endoglin and interleukin (IL)-1α/-1β in sera of 85 MS females, including 15 women with known low AMH level as a marker of ovarian reserve, compared to 63 healthy controls.Groups did not differ with respect to age, smoking habits, BMI, and use of oral contraceptives. MS females showed significantly increased endoglin values compared to healthy controls. Remarkable, the highest endoglin values were found in subjects with low AMH. AOA were neither detectable in MS patients nor control subjects. IL-1α and IL-1β levels did not differ between groups.Our data established no relevance of IL-1α/-1β or AOA in ovarian insufficiency/dysfunction but suggests the involvement of endoglin in RRMS.

Serum Anti-Müllerian Hormone Concentration in Young Women with Chronic Kidney Disease on Hemodialysis, and After Successful Kidney Transplantation

Background/Aims: In women with chronic kidney disease (CKD) fertility abnormalities occur frequently. Anti-Müllerian hormone (AMH) inhibits excessive recruitment of primordial follicles. The aim of the study was to evaluate the serum AMH concentration in women on hemodialysis and after kidney transplantation (KTx). Methods: 46 hemodialysed women and 14 with CKD about to undergo kidney transplantation were enrolled into the study. The control group consisted of 40 healthy women. In all subjects serum concentration of AMH was determined (in chronic hemodialysis women and in control group once, and in women after KTx immediately before surgery, and 3 times after the transplantation). Results: Serum AMH concentration in hemodialysed women and in the control group did not differ significantly, while in hemodialysed women with regular menstrual cycles it was significantly lower than in the control group: 2.20 (1.08-3.55ng/ml) and 3.30 (1.80-6.10ng/ml) respectively, (p=0.02). In the KTx group, a significant decrease in serum AMH concentration was found from 3.30ng/ml (2.20-6.50ng/ml) at baseline to 1.90ng/ml (1.30-2.40ng/ml) at 6 months after KTx (p=0.007). Conclusions: 1. Significantly lower serum AMH concentration was found in the regularly menstruating CKD women on hemodialysis in comparison with the healthy controls. 2. Serum AMH decreased significantly after successful KTx.

Differences in the Follicular Morphology of Young and Aged Bitches and Their Correlation with the Anti-Müllerian Hormone

This study aimed to investigate the structural, morphological and cellular differences of follicles at different stages of follicular development as well as to determine the correlation of the ovarian follicle population with serum Anti-Mullerian Hormone (AMH) levels in young and aged bithches. Sixteen bitches were divided into two groups according to their ages. Group A included young bitches aged 2 years (n=8) while Group B constituted of those aged 8 to 10 years (n=8). Diameters of the primordial, primary and preantral follicles were found to be significantly larger in Group B, in comparison to Group A. In Group A, the mean number of granulosa cells was 91.65±2.23 in the secondary follicles and 301.31±4.16 in the preantral follicles. In Group B, the same values were found to be 89.46±2.68 and 270.25±3.54, respectively. The mean serum AMH levels in Group A and Group B were 0.233±0.046 ng/mL and 0.099±0.008 ng/mL, respectively (P<0.05). In conclusion, the results indicated that the number of primordial and primary follicles as well as the numbers of granulosa cells in secondary and preantral follicles decreased with advanced age which resulted in lower serum AMH levels in aged bitches. The results suggested that the AMH, which is used as a fertility parameter in humans, could also be used for the same purpose in dogs.

Congenital Bilateral Anorchia : A Study of 5 Cases in Jordan = متلازمة اختفاء الخصيتين : دراسة لخمسة حالات في الأردن

We report the clinical and hormonal findings in 5 cases of bilateral anorchism. Five male patients aged 3-5 years presented with suspected cryptorchidism. Physical examination, hormonal, imaging, chromosomal, and molecular analyses of these cases were performed. Ultrasonography of the pelvis and magnetic resonance of the abdomen were performed and failed to show any true testicular tissue or showed only atrophied suspicious testicular tissue. Chromosomal analysis revealed a normal male karyotype and molecular analysis did not reveal mutations or polymorphisms in the SRY gene. The basal FSH and LH levels were increased, and there were increase in response to gonadotropin-releasing hormone test, testosterone levels failed to increase after hCG administration. Lastly, surgical exploration confirmed the absence of testicular structure in three of them. Diagnostically, the very low anti Mullerian hormone level combined with the lack of testosterone response to hCG are the hormonal hallmarks of bilateral congenital anorchia.

Antimüllerian hormone and pregnancy loss from the Effects of Aspirin in Gestation and Reproduction trial

To evaluate if antimüllerian hormone (AMH) is associated with pregnancy loss. Prospective cohort study within a block-randomized, double-blind, placebo-controlled trial of low-dose aspirin. Not applicable. Women (n = 1,228) were of ages 18-40years with a history of one to two pregnancy losses and were actively attempting pregnancy without fertility treatment. Not applicable. Pregnancy loss. Relative risks (and 95% confidence interval [CIs]) of human chorionic gonadotropin (hCG)-detected and clinical pregnancy loss were assessed with the use of log binomial models with robust variance and inverse probability weights adjusted for age, race, body mass index, income, trial treatment assignment, parity, number of previous losses, and time since most recent loss. AMH levels were defined as: low (<1.00ng/mL; n = 124), normal (referent; 1.00-3.5ng/mL; n = 595), and high (>3.5ng/mL; n = 483). Of the 1,202 women with baseline AMH data, 19 (17.3%) with low AMH experienced a clinical loss, compared with 61 (11.4%) with normal AMH and 50 (11.8%) with high AMH levels. Low or high AMH levels, compared with normal AMH, were not associated with clinical loss. Results for hCG-detected pregnancy loss mirrored those of clinical loss. AMH values were not associated with hCG-detected or clinical pregnancy loss in unassisted conceptions in women with a history of one to two previous losses. Our data do not support routine AMH testing for prediction of pregnancy loss. NCT00467363.

Iron stores and obesity are negatively associated with ovarian volume and anti-Müllerian hormone levels in women with polycystic ovary syndrome

ObjectiveObesity and insulin resistance are associated with increased iron stores, but have conflicting effects on ovarian reserve in women with polycystic ovary syndrome (PCOS). Iron-catalyzed oxidative stress might be detrimental to ovarian tissue and granulosa cell function. In this study we determined the association between body iron stores, obesity, and ovarian reserve in women with PCOS. Materials and MethodsOne hundred and fifty-six women diagnosed with PCOS according to Rotterdam criteria and 30 normoweight healthy control women were enrolled in this cross-sectional study. Ovarian volume, total antral follicle count, and the anti-Müllerian hormone (AMH) level were measured as an indicator of ovarian reserve. ResultsFerritin and transferrin-bound iron levels were significantly higher in women with PCOS than normoweight controls. Obese women with PCOS had higher ferritin levels (p = 0.006), but lower AMH levels (p < 0.0001) than nonobese women with PCOS. Using univariate analysis, the AMH level and mean ovarian volume were inversely related to the ferritin level, homeostasis model assessment of insulin resistance, and body mass index in women with PCOS. Body mass index and ferritin level remained significantly correlated with a lower AMH level and reduced ovarian volume, respectively, after considering other confounding variables. ConclusionAn elevated ferritin level and obesity were negatively associated with ovarian volume and the AMH level, respectively, in women with PCOS.

Low antimullerian hormone levels may be associated with cardiovascular risk markers in women with diminished ovarian reserve

There is growing evidence that diminished ovarian reserve (DOR) may be associated with cardiovascular disease (CVD). The aim of the study was to investigate whether there was any relationship between antimullerian hormone (AMH) and CVD risk markers in the study.Ninety women with DOR and 90 women with normal ovarian reserve (NOR) attending the infertility unit at XXXX, were enrolled in the study. CVD risk markers such as insulin resistance [defined by the homeostasis model assessment ratio (HOMA-IR)], C-reactive protein (CRP), low density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) were assessed. HOMA-IR, CRP, TG, LDL levels were higher and HDL and AMH were lower among patients with DOR compared with controls (p < 0.05, for all). There were positive associations between low AMH and HOMA-IR, CRP, TG, LDL levels and a negative correlation with HDL (p < 0.05, for all). However, multivariate logistic regression analysis showed that HOMA-IR, CRP, TG and HDL were independent variables that were associated with low AMH.There was a close relationship between low AMH and CVD risk markers in the study. Further studies with larger groups are needed to investigate the nature of this link in these patients.