Premature and Early Menopause in Relation to Cardiovascular Disease.

Postmenopausal women have an increased risk for cardiovascular diseases. It has been postulated that the loss of ovarian function and subsequent deficiency of endogenous estrogens after menopause contributes to this elevated risk of cardiovascular disease in postmenopausal women. Compared with woman entering menopause at the mean age of 51 years, in women with early menopause or premature ovarian insufficiency the risk for cardiovascular disease is even greater. These women lack the cardioprotective effect of endogenous estrogens for many more years than do women entering natural menopause. The majority of data assessing the risk of cardiovascular disease in relation to age at menopause and specifically premature menopause are derived from large epidemiological cohort studies. In addition, observations in women undergoing bilateral oophorectomy at an early age provide convincing evidence regarding association between early menopause or POI and the development of cardiovascular events and mortality. Moreover, genetic variants associated with earlier age at menopause have also been found to increase the risk of cardiovascular events in women. It has been substantiated that hormone replacement therapy (HRT) decreases the risk for ischemic heart disease and eliminates the increased cardiovascular disease mortality. It is therefore crucial to start HRT as soon as possible, particularly in women with premature ovarian insufficiency.

The role of anti-Müllerian hormone in the classification of anovulatory infertility.

OBJECTIVE: The World Health Organization (WHO) has defined three classes of anovulatory infertility, based on serum gonadotrophin and oestradiol levels: low gonadotrophin and oestradiol levels in women with WHO 1 anovulation, normal hormone levels in WHO 2 anovulation and high gonadotrophin but low oestradiol levels in WHO 3 anovulation. The number of follicles on the ovary also seems to be different in the three classes of anovulatory infertility. Serum anti-Müllerian hormone (AMH) levels correlate well with the number of pre-antral and small antral follicles. The objective of our study was to investigate whether a single AMH measurement might simplify the classification of the WHO classes of anovulatory dysfunction. STUDY DESIGN: In a tertiary hospital, 1863 patients with either oligomenorrhea or secondary amenorrhea were recruited. Standardized screening was performed, including transvaginal ultrasound and serum AMH measurement. Serum AMH levels were compared with those in 348 age-matched controls. RESULTS: Serum AMH levels were slightly elevated in women with hypogonadotropic anovulation (n=128) (P<0.001) as compared with controls. Normogonadotropic anovulatory women (n=1.465) had distinctly higher serum AMH levels than controls (P<0.001) and serum AMH levels were low in women with hypergonadotropic anovulation (n=270) (P<0.001). Although median AMH levels were distinctly different in each class of anovulatory dysfunction, serum AMH levels were comparable in hypogonadotropic women and normogonadotropic women without polycystic ovary syndrome. CONCLUSION: The clinical applicability of serum AMH as a diagnostic tool to differentiate between the different classes of anovulatory dysfunction seems to be limited to the prediction of hypergonadotropic anovulation.

Pregnancy outcome of non-anonymous oocyte donation: a case-control study.

OBJECTIVE: To evaluate the maternal and neonatal outcome of non-anonymous oocyte donation compared to in vitro fertilization. Study design We compared 84 oocyte donation pregnancies with a 251 matched in vitro fertilization cohort. Maternal and neonatal outcomes were retrieved from a nationwide perinatal registry. Oocyte donation and in vitro fertilization pregnancies were matched for maternal age, study center, ZIP code and embryo transfer date. Both maternal and neonatal complications and outcome were compared between oocyte donation and in vitro fertilization with univariate and multivariate logistic regression analyses, adjusting for maternal age, donor age, socio-economic status, ethnicity, and parity. RESULTS: In total, 277 women underwent 541 oocyte donation cycles. The median recipient age was 34.9 years (IQR: 31.5-38.5), while the median donor age was 34.4 years (IQR: 31.7-37.0). Clinical pregnancy rate was 26.6%, which is comparable to standard in vitro fertilization treatment. Donor age in years (OR 0.93, 95% CI 0.88-0.99) and a previous pregnancy of the recipient (OR 1.69, 95% CI 1.02-2.78) were significantly associated with clinical pregnancy rate. Both singleton and multiple oocyte donation pregnancies were associated with pregnancy-induced hypertension compared with in vitro fertilization singleton and multiple pregnancies (OR 1.99, 95%CI 1.02-3.89, OR 6.43, 95% CI 1.67-24.72, respectively). No significant differences in neonatal outcome were observed. CONCLUSION: Oocyte donation pregnancies are associated with an increased incidence of pregnancy-induced hypertension compared with age-matched in vitro fertilization controls. However, no significant differences in neonatal outcome were observed between oocyte donation and in vitro fertilization.

Levels of serum anti-Müllerian hormone, a marker for ovarian reserve, in women with rheumatoid arthritis.

OBJECTIVE: Fertility is reduced in women with rheumatoid arthritis (RA), even before diagnosis. This may be due to a diminished ovarian reserve. The current study examined serum levels of anti-Müllerian hormone (AMH), the most reliable endocrine marker for ovarian reserve, in early RA patients and the influence of disease activity and methotrexate (MTX) use on AMH concentrations. METHODS: Serum AMH levels were measured in 72 women with recent-onset RA ages 18-42 years and compared to 509 healthy women. The association between AMH and rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), erosions, C-reactive protein (CRP) level, disease activity (Disease Activity Score in 28 joints [DAS28]), and use of MTX was assessed. RESULTS: At diagnosis, age-adjusted serum AMH levels did not differ significantly between patients and controls (P = 0.254). AMH levels were not related to the presence of RF (P = 0.487), anti-CCP (P = 0.686), or erosions (P = 0.350), and showed no significant correlation with CRP levels (r = -0.207, P = 0.083) or disease activity scores (DAS28; r = 0.007, P = 0.955). After 6 months of treatment, AMH levels in patients (n = 53) were lower than at the time of diagnosis (P < 0.001), but did not differ from controls (P = 0.741). There was no significant difference in AMH values after 6 months of treatment between patients who did (n = 31) or did not (n = 22) receive MTX (P = 0.287). CONCLUSION: AMH levels in women with early RA are comparable to those of healthy controls, indicating that the reduced fertility in this patient group is not caused by diminished ovarian reserve. AMH levels are not affected either by disease activity or by short-term MTX use.

Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency.

Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a disorder of infertility characterized by amenorrhoea, low estrogen levels and increased gonadotropin levels in women aged <40 years. POI is the result of premature exhaustion of the follicle pool or can be attributed to follicular dysfunction, for example, owing to mutations in the follicle-stimulating hormone receptor or steroidogenic cell autoimmunity. Moreover, advances in cancer therapeutics over the past decades have led to increasing survival rates for both paediatric and adult malignancies. Given the gonadotoxic effect of many cancer treatments, more women develop POI. A marker that predicts whether women are at risk of POI would, therefore, aid in early diagnosis and fertility counselling. Anti-Müllerian hormone (AMH), a growth factor produced solely by small, growing follicles in the ovary, might constitute such a marker, as serum levels of this hormone correlate strongly with the number of growing follicles. In addition, AMH could potentially help assess the progression of ovarian senescence, as serum AMH levels are independent of hypothalamic-pituitary-gonadal axis function and decrease to undetectable levels at menopause. In cancer survivors, serum AMH levels correlate with the extent of gonadal damage. In this Review, we provide an overview of the current studies that have measured AMH in women with POI of various aetiologies and discuss its possible application as a marker to determine ovarian reserve.

Serum anti-Müllerian hormone and inhibin B concentrations are not useful predictors of ovarian response during ovulation induction treatment with recombinant follicle-stimulating hormone in women with polycystic ovary syndrome.

OBJECTIVE: To describe changes of anti-Müllerian hormone (AMH) and inhibin B during low-dose gonadotropin ovulation induction (OI) treatment in women with polycystic ovary syndrome (PCOS), and thus disturbed selection of the dominant follicle. DESIGN: Observational study. SETTING: A referral fertility clinic. PATIENT(S): Women with PCOS (n = 48) and normo-ovulatory women (n = 23). INTERVENTION(S) AND MAIN OUTCOME MEASURE(S): Serum AMH, inhibin B, FSH, and E(2) concentrations were measured at start of stimulation, on the day of follicle selection, and at administration of hCG during OI cycles and were compared with concentration measured during the normal menstrual cycle. RESULT(S): Development of a single dominant follicle was observed in 92% of all OI cycles, reflected by similar E(2) concentrations compared with those in spontaneous cycles. AMH concentrations were constant during low-dose ovarian stimulation. Inhibin B concentrations remained elevated in patients with PCOS, suggesting prolonged survival of small antral follicles, whereas in controls inhibin B concentrations declined during the late follicular phase. CONCLUSION(S): The lack of change in AMH and inhibin B concentrations suggest that follicle dynamics during low-dose stimulation seem different from those during controlled ovarian hyperstimulation. In addition, constant AMH and inhibin B levels suggest that neither AMH nor inhibin B is an accurate marker of ovarian response after low-dose gonadotropin OI in patients with PCOS.