Search

BACKGROUND: Anti-Müllerian hormone (AMH), produced by growing pre-antral and early antral ovarian follicles, has been shown to be a useful marker for ovarian ageing. Serum AMH concentrations are elevated during reproductive life in anovulatory women, especially in those patients exhibiting polycystic ovaries (PCO). The current study was designed to investigate whether the decrease in AMH serum concentrations over time is different comparing women with normogonadotrophic anovulation [World Health Organization (WHO) group 2 (including polycystic ovary syndrome (PCOS)] and normo-ovulatory controls. METHODS and RESULTS: AMH serum levels were assessed on two occasions in 98 patients suffering from WHO 2 anovulatory infertility as well as in 41 normo-ovulatory premenopausal women. Median time interval between both visits was 2.6 years (range 0.3–9.0) for WHO 2 patients compared with 1.6 years (range 1.0–7.3) in controls. Serum AMH concentrations were significantly (P<0.0001) elevated on both occasions in WHO 2 patients (AMH1, median = 7.5 μg/l, range 0.1–35.8; and AMH2, median = 6.7 μg/l, range 0.0–30.6) compared with controls (AMH1, median = 2.1 μg/l, range 0.1–7.4; and AMH2, median = 1.3 μg/l, range 0.0–5.0). Regression analysis, corrected for age, indicated a significant relative decrease in serum AMH concentrations over time for both groups (P<0.001). However, the decline in serum AMH in WHO 2 patients was significantly less compared with controls (P=0.03). CONCLUSION: The present longitudinal study shows that serum AMH concentrations decrease over time both in women presenting with WHO 2 anovulatory infertility and in normo-ovulatory controls. The decrease in WHO 2 patients is less pronounced despite distinctly elevated concentrations. This observation may suggest retarded ovarian ageing and hence a sustained reproductive life span in these patients. [ABSTRACT FROM AUTHOR]

A 13-year-old girl was referred because of progressive abdominal pain caused by ovarian torsion and giant ovarian cysts. Secondary sexual characteristics were absent. Hormone analysis revealed markedly elevated serum levels of progesterone and 17-hydroxyprogesterone in combination with very low peripheral concentrations of C19 steroids (dehydroepiandrosterone and androstenedione) and estrogens. Serum concentrations of FSH and LH exceeded the upper limit of normal levels in adult women. The patient's 16-year-old 46,XY sibling showed a female phenotype with similar hormonal disturbances. Both siblings were found to be compound heterozygotes for two mutations in the CYP17 gene: an R347C mutation in one allele and a 25-base pair deletion in exon 1 in the other. The resulting block in 17,20-lyase activity caused an inability to synthesize androgens and estrogens, and increased levels of gonadotrophins due to a lack of negative feedback. The increased levels of gonadotrophins most likely stimulated growth of the ovarian cysts. The administration of a GnRH antagonist reduced the size of the cysts within a few weeks. At present, the girl is being treated with a combination of a GnRH agonist and hormone replacement therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Polycystic ovaries display an increased number of pre-antral and antral follicles compared with normal ovaries, suggesting that early and late follicle development are disturbed. The pathophysiology of this process is poorly understood. Since the transforming growth factor β family members, anti-Müllerian hormone (AMH) and bone morphogenetic proteins (BMPs), inhibit FSH sensitivity, their signalling may contribute to the aberrant follicle development in these women. Here, we investigated the role of ALK2, a type I receptor for AMH/BMP signalling, in PCOS using a genetic approach. METHODS Seven single nucleotide polymorphisms in the ACVR1 gene, encoding ALK2, were genotyped in 359 PCOS patients and 30 normo-ovulatory and 3543 population-based control women, and haplotypes were determined. Subsequently, the association of ACVR1 variants with ovarian parameters and hormone levels was investigated. RESULTS The polymorphisms rs1220134, rs10497189 and rs2033962 and their corresponding haplotypes did not show different frequencies from controls, but were associated with AMH levels in PCOS women (P = 0.001, P = 0.002 and P = 0.007, respectively). Adjustment for follicle number revealed that the association with AMH levels was, in part, independent from follicle number, suggesting that variants in ACVR1 also influence AMH production per follicle. CONCLUSIONS Genetic variation within ACVR1 is associated with AMH levels and follicle number in PCOS women, suggesting that ALK2 signalling contributes to the disturbed folliculogenesis in PCOS patients. [ABSTRACT FROM AUTHOR]

BACKGROUND The aim of this study was to evaluate the long-term gonadal sequelae after treatment for childhood Hodgkin’s lymphoma with combination chemotherapy, using up to date fertility parameters and andrological evaluation, including for the first time inhibin B. METHODS There were 56 male patients treated from 1974–1998 for childhood Hodgkin’s lymphoma with combination chemotherapy ABVD or EBVD (adriamycin/epirubicin, bleomycin, vinblastine, dacarbazine) with or without MOPP (mechlorethamine, vincristin, prednisone, procarbazine) with the intention to avoid radiotherapy. These men were studied 15.5 years (range 5.6–30.2 years) after cessation of therapy. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone, sex hormone-binding globulin (SHBG), sperm concentration and sperm DNA integrity were determined. RESULTS In men treated with MOPP, median FSH and LH were significantly increased (P P P r = 0.86; P CONCLUSIONS The use of MOPP chemotherapy causes permanent gonadal damage in the far majority of male survivors of childhood Hodgkin’s lymphoma and inhibin B is the most valuable serum marker for gonadal function. [ABSTRACT FROM AUTHOR]

: BACKGROUND Ovarian failure as a complication of uterine artery embolization (UAE) for symptomatic uterine fibroids has raised concerns about this new treatment modality. : METHODS We investigated the occurrence of ovarian reserve reduction in a randomized trial comparing UAE and hysterectomy by measuring follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH). A total of 177 pre-menopausal women with menorrhagia due to uterine fibroids were included (UAE: n = 88; hysterectomy: n = 89). FSH and AMH were measured at baseline and at several time-points during the 24 months follow-up period. Follow-up AMH levels were also compared to the expected decrease due to ovarian ageing during the observational period. : RESULTS FSH increased significantly compared to baseline in both groups after 24 months follow-up (within group analysis: UAE: + 12.1; P = 0.001; hysterectomy: + 16.3; P < 0.0001). No differences in FSH values between the groups were found (P = 0.32). At 24 months after treatment the number of patients with FSH levels > 40 IU/l was 14/80 in the UAE group and 17/73 in the hysterectomy group (relative risk = 0.75; P = 0.37). AMH was measured in 63 patients (UAE: n = 30; hysterectomy: n = 33). After treatment AMH levels remained significantly decreased during the entire follow-up period only in the UAE group compared to the expected AMH decrease due to ageing. No differences were observed between the groups. : CONCLUSIONS This study shows that both UAE and hysterectomy affect ovarian reserve. This results in older women becoming menopausal after the intervention. Therefore, the application of UAE in women who still wish to conceive should only be considered after appropriate counselling. [ABSTRACT FROM AUTHOR]

BACKGROUND In mice, anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment and decreases FSH sensitivity. Little is known about the role of AMH in human ovarian physiology. We hypothesize that in women AMH has a similar role in ovarian function as in mice and investigated this using a genetic approach. METHODS The association of the AMH Ile49Ser and the AMH type II receptor (AMHR2) −482 A > G polymorphisms with menstrual cycle characteristics was studied in a Dutch (n = 32) and a German (n = 21) cohort of normo-ovulatory women. RESULTS Carriers of the AMH Ser49 allele had higher serum estradiol (E2) levels on menstrual cycle day 3 when compared with non-carriers in the Dutch cohort (P = 0.012) and in the combined Dutch and German cohort (P = 0.03). Carriers of the AMHR2 −482G allele also had higher follicular phase E2 levels when compared with non-carriers in the Dutch cohort (P = 0.028), the German cohort (P = 0.048) and hence also the combined cohort (P = 0.012). Women carrying both AMH Ser49 and AMHR2 −482G alleles had highest E2 levels (P = 0.001). For both polymorphisms no association with serum AMH or FSH levels was observed. CONCLUSIONS Polymorphisms in the AMH and AMHR2 genes are associated with follicular phase E2 levels, suggesting a role for AMH in the regulation of FSH sensitivity in the human ovary. [ABSTRACT FROM AUTHOR]