Inhibin B in adolescents and young adults with Turner syndrome

Author(s):  
Maria Francesca Messina ◽  
Tommaso Aversa ◽  
Giuseppina Salzano ◽  
Daria Costanzo ◽  
Concetta Sferlazzas ◽  
...  

AbstractPrimary gonadal failure may occur in most individuals with Turner syndrome (TS). Since ovaries in TS girls undergo premature apoptosis and cryopreservation of ovarian tissue is now feasible, it would be useful to identify a reliable marker of ovarian reserve in these patients. We planned to evaluate ovarian function in a group of TS patients by measuring both traditional markers and inhibin B and to compare these results with those of a control group.We enrolled 23 patients with TS and 17 age-matched healthy girls. The median age of our TS patients was 17.6 years. Three out of the 23 patients (13%) showed spontaneous pubertal development and regular menstrual cycles; the remaining 20 (86.9%) presented with primary amenorrhea.The median level of inhibin B in the TS patients with primary amenorrhea was 42 pg/mL and did not differ significantly among the different subgroups in relation to karyotype. The median inhibin B level in the control group was significantly higher than in the TS girls with primary amenorrhea (83 vs. 42 pg/mL, p<0.00001). In the three patients with TS and spontaneous menstrual cycles, the inhibin B levels were significantly higher when compared to the values of the TS girls with primary amenorrhea.TS patients with primary amenorrhea have significantly lower levels of inhibin B than TS girls with spontaneous puberty and healthy controls. Inhibin B does not correlate with follicle-stimulating hormone/luteinizing hormone. If our results are confirmed in further studies, inhibin B could become a first-line screening test for assessing ovarian reserve and a longitudinal marker of the possible decline of ovarian function in TS.

2018 ◽  
Vol 75 (7) ◽  
pp. 644-650
Author(s):  
Olivera Dzatic-Smiljkovic ◽  
Mladenko Vasiljevic ◽  
Ivana Rudic ◽  
Jelena Vugdelic ◽  
Aleksandar Ristic ◽  
...  

Background/Aim. Endometriosis is a gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. The aim of this paper was to determine the effect of laparoscopic cystotomy and cystectomy on ovarian function, as well as to compare these two methods in terms of qualitative and quantitative damage to the ovaries, achieved pregnancies and recurrence. Methods. The prospective study, conducted in ?Narodni Front? Obstetrics and Gynaecology Clinic in Belgrade at the Endoscopic Infertility Treatment Ward, included a total of 150 patients. The study group was represented by 100 patients who underwent a surgical treatment of endometrial ovarian cysts. The patients in the study group were divided into 2 subgroups: Subgroup I consisted of 50 patients who underwent a laparoscopic cystotomy (incision of the cyst and thermal coagulation) and subgroup II which included 50 women who underwent a laparoscopic cystectomy. The control group consised of patients who underwent a surgery due to tubal factor infertility. The following parameters of the ovarian function were tested: the ovarian volume, the antral follicle count, the presence of the preovulatory follicle on the operated ovary, the serum levels of anti- M?llerian hormone (AMH), follicle-stimulating hormone (FSH), ovarian tumor marker (Ca 125), inhibin B, as well as the rate of achieved pregnancies one year after the surgery. Results. The ovarian volume and the antral follicle count as well as the FSH values were significantly higher in the control group in comparison with the patients in the study group. There were no significant differences in the ovarian volume, the antral follicle count, the AMH values and inhibin B values in the study group between the patients with cystectomy and those with the incision and coagulation of the cyst. Conclusion. Both surgical techniques diminished the ovarian reserve: cystectomy was more aggressive method in terms of the damage inflicted on the ovarian tissue, and incision with coagulation carried a higher risk of recurrence.


2011 ◽  
Vol 96 (4) ◽  
pp. 1136-1144 ◽  
Author(s):  
Femi Janse ◽  
Jacques Donnez ◽  
Ellen Anckaert ◽  
Frank H. de Jong ◽  
Bart C. J. M. Fauser ◽  
...  

Abstract Context: In young women, some treatments for cancer or other conditions (such as sickle cell anemia) may give rise to primary ovarian insufficiency. Ovarian transplantation is one of the available options for fertility preservation, with highly variable pregnancy rates. Objective: The objective of the study was to investigate markers of ovarian reserve and ovarian function in women up to 7 yr after orthotopic ovarian transplantation. Secondary objectives were to assess the relationship between markers of ovarian reserve and pregnancy rate along with the duration of ovarian function. Design: This was a prospective cohort study in 10 women, with a mean follow-up of 2.5 yr. Setting: The study was conducted at a university hospital in Brussels, Belgium. Patients: Patients included 10 women who were about to receive or had previously received gonadotoxic treatment. In seven women cryopreservation of ovarian tissue was performed before starting treatment. Subsequently autografts were orthotopically transplanted in these women. Three women, who had already developed primary ovarian insufficiency due to treatment, underwent orthotopic transplantation of ovarian allograft tissue originating from their human leukocyte antigen-compatible sisters. Main Outcome Measures: Serum concentrations of FSH, LH, estradiol, inhibin B, and anti-Müllerian hormone (AMH) were measured. Results: On average, first menses took place after 4.7 months. Duration of graft functioning varied from 2 to more than 60 months. FSH concentrations remained elevated, whereas estradiol levels normalized and AMH was low to undetectable. Inhibin B varied among women and was not associated with the duration of ovarian function (hazard ratio 0.966, 95% confidence interval 0.881–1.059). Two spontaneous pregnancies occurred. Endocrine characteristics were not significantly different in these women. Conclusions: Low AMH and inhibin B concentrations may suggest decreased ovarian reserve in women after ovarian transplantation. AMH and inhibin B levels may not be associated with the duration of ovarian graft function or probability to achieve a pregnancy.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH &gt; 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable


2012 ◽  
Vol 97 (9) ◽  
pp. E1766-E1773 ◽  
Author(s):  
Elbrich P. C. Siemensma ◽  
A. A. E. M. (Janielle) van Alfen-van der Velden ◽  
Barto J. Otten ◽  
Joop S. E. Laven ◽  
Anita C. S. Hokken-Koelega

Context: The etiology of hypogonadism in girls with Prader-Willi syndrome (PWS) remains uncertain. Objectives: The aim of the study was to evaluate gonadal function longitudinally in girls and female adolescents with PWS. Measurements: We performed a longitudinal assessment of anti-Müllerian hormone (AMH), gonadotropins, estradiol (E2), inhibin B and A, and pubertal development in girls and female adolescents with PWS. Patients and Methods: Sixty-one girls participating in the Dutch PWS Cohort study participated in the study. Serum AMH, gonadotropins, E2, and inhibin B and A levels were compared with reference values. Results: AMH levels in girls and female adolescents with PWS were comparable to reference levels between 6 months and 22 yr of age. From 10 yr of age, FSH and LH levels increased to above the 5th percentile compared to reference levels. E2 and inhibin B levels were in the low normal range in the majority, and inhibin A levels were low but detectable in almost half the female adolescents with PWS. The median age at puberty onset was comparable, but the median ages at attaining Tanner M3 (P = 0.05) and M4 (P &lt; 0.0001) were significantly higher in girls with PWS than in healthy references. Conclusion: Our study shows that the primordial follicle pool and number of small antral follicles are conserved in girls and female adolescents with PWS. We found no classical hypogonadotropic hypogonadism. However, maturation of follicles and progression of pubertal development are impaired, which might be due to dysregulation of LH secretion. Because these impairments are not absolute, ovulation and thus conception cannot be ruled out in individual female adolescents with PWS.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Miller ◽  
Y Pasternak ◽  
C Dornstein ◽  
E Haiki. Herzberger ◽  
N Zada ◽  
...  

Abstract Study question Is high physical activity (HPA) associated with low ovarian reserve in normo-ovulatory, reproductive-age women? Summary answer HPA does not affect ovarian reserve negatively. What is known already HPA is associated with menstrual irregularities and subsequent potential infertility, probably through hypothalamic neuroendocrine pathways. However, it is not yet known whether HPA influences the ovarian reserves of normo-ovulatory, reproductive-age women. Study design, size, duration This observational, cross-sectional study compared 30 professional female athletes who were engaged in HPA for at least 3 years prior to study recruitment, with high International Physical Activity Questionnaire (IPAQ) scores and 30 women who did not engage in physical activity. The study was conducted at a tertiary medical center from 2017–2020. Participants/materials, setting, methods Physically active, normo-ovulatory women (n = 30), ages 20–35 years were recruited from The Wingate Institute, the Israeli National Institute for Sport Excellence. Non-physically active women (n = 30), matched by age and BMI to the HPA group, were recruited from the hospital staff. Both groups were evaluated for ovarian reserve markers on day 2–5 of the menstrual cycle, including follicular stimulating hormone (FSH), antral follicle count (AFC), anti-Mullerian hormone (AMH) and Inhibin B. Main results and the role of chance The average age of the athletes (HPA group) was 30.1±2.1 years and of the nonactive (control) group 31.6±3.8 years (p = 0.071). BMI of the 2 groups was similar (22.6±2.4 vs. 21.3±2.6; p = 0.075) for the HPA and control groups, respectively. Regarding ovarian reserve, no significant differences were observed between the HPA group and the control group with respect to FSH (p = 0.304), AFC (p = 0.27), AMH (0.507) or Inhibin B (p = 0.074). For the HPA group, older age at menarche was positively associated with AFC (p = 0.008) and AMH (p = 0.009) and not with FSH levels (p = 0.313). For the nonactive group, no significant association between age at menarche and FSH levels, AFC or AMH was found (p = 0.433, p = 0.274 and p = 0.163, respectively). Additionally, for the HPA group, duration of physical activity per week (hours) was not significantly associated with FSH levels, AFC or AMH (p = 0.619, p = 0.608 or p = 0.997, respectively). Limitations, reasons for caution Although we investigated the ovarian reserves of 30 women engaged in HPA, a larger cohort would provide more information. Information on diet and sleep habits was not evaluated and may result in some confounding. Moreover, it would be more informative if we also followed these women regarding fecundability and fertility. Wider implications of the findings: This study demonstrated that HPA may not negatively affect ovarian reserve markers. These findings may provide reassurance for women who are engaged in HPA and attempting pregnancy. Further research needs s to be confuted. Trial registration number 0247–16


2016 ◽  
Vol 34 (22) ◽  
pp. 2568-2574 ◽  
Author(s):  
Isabelle Demeestere ◽  
Pauline Brice ◽  
Fedro A. Peccatori ◽  
Alain Kentos ◽  
Jehan Dupuis ◽  
...  

Purpose We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. Patients and Methods A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Results Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m2 (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). Conclusion To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug’s benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1536.2-1537
Author(s):  
Z. Alekberova ◽  
R. Goloeva ◽  
M. Cherkasova ◽  
A. Lila

Background:Access to assays of circulating anti-Mullerian hormone (AMH) levels has opened a new page in the assessment of ovarian function and fertility in various diseases, including rheumatic diseases (RDs). The definition of AMH as a marker of ovarian reserve significantly simplified its interpretation as well as measuring the contribution of the disease itself to the patients’ infertility.Objectives:To evaluate the effects of the disease and it’s treatment on serum AMH levels for Behcet’s disease (BD), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic scleroderma (SSD).Methods:The study included 73 patients with RDs from 18 to 40 years: 42 patients with BD, 12 with SLE, 11 with RA, 8- with SSD, the control group consisted of 15 healthy women. Enzyme-linked immunosorbent assay (ELISA) was used to measure AMH levels. Parametric and nonparametric statistical methods of Statistica 8.0 package were used for statistical processing of data.Results:Mean age in BD patients was 30.0 years, in SLE and RA -33.5 years, in SSD - 35.0 years, and 32.0 years in the control group. The average disease duration was 4.5 years, 11.5 years, 4.0 years and 6.0 years, respectively.BD, n=42SLE, n=12RA, n=11SSD, n=8Control, n=15Mean age, years30,0[26;35]33.5[29;38]33,5[24;36]35,0[28;40]32,0[26;35]Average disease duration, years4,5[2,6;9,0]11,5[2,8;18]4,0[4,0;6,0]6,0[2,0-10,0]-Mean AMH level, ng/ml2,5[1,1;3,7]3,5[0,4-7,1]3,35[2,0;7,6]2,5 [0,3;7,1]3,1[1,9;5,4]There were no significant differences in the mean AMH levels between the groups. No association between AMG levels and clinical manifestations, disease activity or duration of rheumatic disease was found. Baseline AMH – in treatment-naïve patients before initiation of any DMARDs was assessed in 11 BD patients. A significant (p>0.05) decrease of AMH levels was established in patients with high SLE activity treated with CP. Of notice, all examined patients were additionally receiving a GEBD -Rituximab.Conclusion:Decreased ovarian function was found in patients with high SLE activity treated with CP with Rituximab.Disclosure of Interests:None declared


2021 ◽  
Vol 10 (22) ◽  
pp. 5217
Author(s):  
Vinnie Hornshøj Greve ◽  
Margit Dueholm ◽  
Linn Salto Mamsen ◽  
Stine Gry Kristensen ◽  
Erik Ernst ◽  
...  

Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ali Doğukan Anğın ◽  
Ebru Çöğendez ◽  
İsmet Gün ◽  
Önder Sakin ◽  
Muzaffer Seyhan Çıkman ◽  
...  

To determine the possible detrimental effects of multiple methotrexate doses has on the ovarian reserve and to determine the beneficial effects of dehydroepiandrosterone supplementation. The rats (n:24) divided into three groups; Group 1: control group, Group 2: dehydroepiandrosterone and methotrexate group (6mg/kg dehydroepiandrosterone dissolved in 0.1 ml sesame seed oil subcutaneously for ten days and 1mg/kg intramuscular methotrexate at the 1st, 3rd, 5th and 7th days) and Group 3: methotrexate group (1mg/kg intramuscular methotrexate at the 1st, 3rd, 5th and 7th day). The groups compared in regards to their histopathological ovarian damage scores and AMH values. It established that multiple methotrexate applications had a considerable effect on reducing vascular congestion in the ovarian tissue. Both in groups 2 and 3 AMH values found to be significantly lower. When this decline in the ovarian reserve examined comparatively; while both the group 2 and 3 reported having a considerable and continuous reduction in the AMH levels correlative to the control group; the primordial, primary and total follicle counts shown to stay statistically the same in the group 2 (p<0.0167). The dehydroepiandrosterone supplementation, while did not have a significant effect on reducing ovarian damage induced by methotrexate, also was not shown to provide any considerable increase in AMH levels. However, prolonged usage of dehydroepiandrosterone by contributing to the antral follicle pool considered promising in increasing the AMH levels conceivably


2022 ◽  
Vol 9 (1) ◽  
pp. 749-758
Author(s):  
Fidelis Ohiremen Oyakhire ◽  
Cedric Odaro ◽  
Enehizena Osaro Ogie ◽  
Eseoghene Valentine Egho ◽  
Joy Akpesiri Egho ◽  
...  

Objective: Anti-Mullerian hormone has been indicated as a novel biomarker for ovarian reserve assessment. This study aimed to determine the comparative advantage of serum levels of AMH, FSH, LH, E2, and  LH/FSH ratio among women with varying menstrual cycles and duration of menstruation.   Material and Method: A total of 90 subjects, which consisted of sixty subjects and thirty healthy subjects as control, were recruited. Blood samples were collected on day 3 of the menstrual cycle and evaluated for ovarian markers using the ELISA technique. All data were analyzed using SPSS version 23.0. Results: AMH and LH/FSH levels were lower in women with varying menstrual cycles than in the control group. FSH, LH, and E2 levels were significantly higher in women with varying menstrual cycles and flow duration than in the control group(P<0.05).  AMH was negatively correlated with age (r= -0.72), BMI( r= -0.4), FSH(r= - 0.3), LH(r = -0.2) (p<0.05) and E2(r= -0.2, p>0.05). Also age was positively correlated with FSH(r=0.5,p<0.05), E2(r=0.3, p<0.05) and BMI(r=0.4, p<0.05). The level of AMH was not significant with cycle length and days of flow(p>0.05). This implies that AMH can be measured independently of the cycle phase. This show that AMH was lower in women with varying menstrual cycle with an increase in gonadotrophin and E2. The strong negative relationship between age and AMH implies that age is determining factor of ovarian reserve.  Conclusion: AMH combined with age and FSH may improve ovarian reserve evaluation, making AMH a better marker


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