Marker Of Ovarian Function Research Articles

Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function

The purpose of the present report was to study the possible relationship between ovarian functionality and the immune response during cystogenesis induced by androgenization with dehydroepiandrosterone (DHEA). Daily injection of DHEA (6 mg/kg body weight) for 20 consecutive days induced ovarian cysts in BALB/c mice. As markers of ovarian function, serum estradiol (E) and progesterone (P) and the ovarian inmunomodulator prostaglandin E (PGE) were analyzed. In order to know how the integrity of the tissue was altered after induction of cystogenesis, the oxidative status was also evaluated. Serum E and P levels, and ovarian PGE concentration, were increased in animals with cysts compared with healthy controls. The oxidant status (quantified by malondialdehyde (MDA) formed after the breakdown of the cellular membrane by free radical mechanisms) was augmented, meanwhile the antioxidant (evaluated by the glutathione (GSH) content) diminished during the induction of cystogenesis. Both immunohistochemical and flow cytometry assays demonstrated that DHEA treatment increased the number of T lymphocytes infiltrating ovarian tissue. Therefore, while ovarian controls showed equivalent expression of CD4+ and CD8+ T cell subsets, injection of DHEA yielded a selective ovarian T cell infiltration as demonstrated by enhanced CD8+ and diminished CD4+ T lymphocyte expression. These results show that the development of cysts involves changes in ovarian function and an imbalance in the oxidant–antioxidant equilibrium. We observed also both an increased and selective T lymphocyte infiltration.

Inhibin B in serum and inhibin A and B in follicular fluid of patients undergoing assisted reproduction techniques: the correlation with ovarian response and the relationship with follicular size, maturity and other hormone concentration

Objective: Previous studies (Hoffmann G 1998, Seifer DB 1999) demonstrate the value of inhibin B as a direct marker of ovarian function. Others (Groome NP 1996, Klein NA 1996) investigate the inhibins levels during the menstrual cycle. The purpose of this study was to a) Determine the posible correlation between inhibin B and ovarian response in term of oocytes retrieved. b) The relationship between intrafollicular inhibins (A and B) from dominant follicle with the follicular size, maturity and other (androstenedione-oestradiol-progesterone) intra-follicular hormone content. Design: comparative-restrospective analysis from patients of our center. Materials and Methods: From May of 2002 to Dicember of 2002, we studied 58 consecutive IVF patients (all of them with normal FSH ((<12mUI/ml) levels and age less than 38 years)) by measuring serum Inhibin(B) day 3 levels on the cycle prior to COH with standard long protocol and stored to measure inhibin(B) after the IVF cycle was completed. Inhibin (A) and (B) was analyzed by double antibody ELISA (Serotec, NC USA) limit of deetection was 15 pg/ml. Intra and interassay COV were less than 10%. The follow up was performed by ultrasound and dosage of serum estradiol. Transvaginal oocyte retrieval was performed 36 hours after the administration of 10.000 UI hCG and the follicular fluyd was stored to measure both inhibins (A), (B) and the other hormone parametres for hormonal study. Results: a. Our results showed an strong significant linear relationship (r=0,67, p≤0,0001) between Inhibin B day 3 basal levels and oocytes aspirated b. In dominant follicle (>16 mm) Inhibin A, estradiol increased and androstenedione decreased with follicular size (r=0,63; p=0,0001) and (r=0,65; p≤0,0001) respectively. View Large Image Figure ViewerDownload (PPT) Conclusion: Day 3 inhibin B levels show us a significant linear relationship with ovarian response and Intrafollicular estradiol, inhibin A concentration increased significantly with follicle size whereas significant inverse relationships were observed for androstenedione and inhibin B not varied consistendly with follicular size. This result are consistent with the fact that the follicular changed from androstenedione to estradiol and inhibin A dominance.

Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3.

The study aim was to compare the relationship between serum anti-Müllerian hormone (AMH) levels and other markers of ovarian function with early antral follicle count on day 3. A total of 75 infertile women was studied prospectively. On cycle day 3, serum levels of AMH, inhibin B, estradiol (E(2)), FSH and LH levels were measured, and the number of early antral follicles (2-10 mm in diameter) estimated at ultrasound scanning to compare the strengths of hormonal-follicular correlations. Median (range) serum levels of AMH, inhibin B, E(2), FSH and LH were 1.39 ng/ml (0.24-6.40), 90 (16-182) pg/ml, 31 (15-111) pg/ml, 7.0 (2.9-19.3) mIU/ml and 4.7 (1.2-11.7) mIU/ml respectively, and follicular count was 12 (1-35). Serum AMH levels were more strongly correlated (P < 0.001) with follicular count (r = 0.74, P < 0.0001) than were serum levels of inhibin B (r = 0.29, P < 0.001), E(2) (r = -0.08, P = NS), FSH (r = -0.29, P < 0.001) and LH (r = 0.05, P = NS). Serum AMH levels were more robustly correlated with the number of early antral follicles than inhibin B, E(2), FSH and LH on cycle day 3. This suggests that AMH may reflect ovarian follicular status better than the usual hormone markers.

The physiology and pathophysiology of inhibin, activin and follistatin in female reproduction.

In the last 2 years, major advances have been made in the understanding of inhibin physiology. Discovery of an inhibin receptor and binding protein has expanded our knowledge of the mechanism whereby inhibin antagonizes activin action. Controlled experimental studies have clarified the regulation and physiology of inhibin A and inhibin B, providing evidence for their use as markers of ovarian function. Clinical studies continue to uphold the use of inhibin as a marker for ovarian cancer, but have not generally supported its use over standard prognostic markers in assisted reproductive technologies. Finally, ongoing work suggests alterations in inhibin and follistatin that may be linked to the pathophysiology of polycystic ovary syndrome. Thus, the mechanism of inhibin action and its role in normal and abnormal ovarian function continues to emerge.

Bone mass and metabolism in women aged 45-55.

Changes in calcium homeostasis and bone mass around the climacteric are poorly understood. We examined relations between endocrine factors and indices of bone mass and metabolism in healthy women approaching the menopause. Cross-section study. Sixty-eight spontaneously menstruating women aged 45-55. Bone density measured at lumbar spine (LS) and femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant forearm using peripheral quantitative computed tomography. We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E2), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion. Using serum FSH level as a marker of ovarian function, 63 subjects could be classified into one of three groups: group A (serum FSH < 10 U/l, n = 29), group B (10-35 U/l, n = 27) and group C (> 35 U/l, n = 7). Bone density fell with declining ovarian function at the LS, FN and forearm trabecular (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68 (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09) pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) mumol/mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) mumol/mol creatinine) excretion were also increased. There were no significant differences in vitamin D metabolites or osteocalcin. Multivariate analysis suggested serum osteocalcin was positively related to physical activity and serum 1,25-dihydroxycholecalciferol levels. Serum free T3 was positively correlated with urinary DPD excretion, and inversely related to serum PTH. In all subjects, serum PTH was related to body weight (r = 0.38, P = 0.002). Declining ovarian function before menopause is accompanied by reductions in bone mass and altered calcium metabolism. Free T3 may regulate bone resorption and indirectly modulate PTH release.

Urinary follicle-stimulating hormone as a biological marker of ovarian toxicity

Reproductive senescence has not been adequately explored as a possible end point for assessing toxicity to the reproductive system. We propose that urinary FSH be used as a biologic marker of ovarian function in women. A urinary marker would facilitate the incorporation of this measure into epidemiologic studies of reproductive toxicity. Although there is some evidence that FSH in serum is a good biologic marker of ovarian reserve, the relationship between serum FSH and urinary FSH has not been adequately explored. We found that urinary FSH and serum FSH were closely correlated in 50 consecutive women seen in clinical practice.

Validation of the dual analyte assay of the oestrone: pregnanediol ratio in monitoring ovarian function

The purpose of this study was to validate the dual analyte system (Boots Celltech Ltd, Slough, UK) as a marker of ovarian function. For this purpose the urinary profile of the ratio of oestrone-3-glucuronide to pregnanediol-3-glucuronide in urine (E13G/PD3G) was compared with plasma concentrations of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone from day 8-24 of the menstrual cycle in 23 women. Daily transvaginal ultrasound was also performed from day 8 of the cycle until sonographic evidence of follicular rupture. The ratio of urinary metabolites exhibited a maximum value close to ovulation. In the majority of cases this coincided with the day of LH peak, and was followed by follicular rupture within the next 24 h in 74% of cases. The assay gives a good marker of ovulation, however, it is unlikely to help in detecting the initiation of the fertile period or the quality of the menstrual cycle.