Stine Aagaard Lunding1, Susanne Elisabeth Pors2, Stine Gry Kristensen2, Jane Alrø Bøtkjær2, Maja Ramløse2, Janni Vikkelsø Jeppesen3, Esben Meulengracht Flachs4, Anja Pinborg3,5, Kirsten Tryde Macklon3, Anette Tønnes Pedersen3,6, Claus Yding Andersen2, Anders Nyboe Andersen3. 1. The Fertility Clinic, Section 4071, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. stine.aagaard.lunding@regionh.dk. 2. Laboratory of Reproductive Biology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 3. The Fertility Clinic, Section 4071, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark. 4. Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark. 5. The Fertility Clinic, Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark. 6. Department of Gynecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract
PURPOSE: To evaluate the association between anti-Müllerian hormone (AMH) and follicle density in infertile women with diminished ovarian reserve (DOR) versus women with normal ovarian reserve? METHODS: Case-control study comparing follicle densities in ovarian cortex from 20 infertile women with DOR (AMH ≤ 5 pmol/L) and 100 controls with presumed normal ovarian reserve. RESULTS: For all women > 25 years, the follicle densities correlated positively with AMH levels. For each single picomole per liter increase in AMH the follicle density increased by 6% (95% CI 3.3-8.5%) when adjusted for age. This was similar for women with DOR and controls. The follicle density was 1.8 follicles/mm3 cortical tissue in women with DOR versus 7.0 in age-paired controls (p = 0.04). The women with DOR had a median AMH of 1.8 pmol/L versus 14.4 pmol/L in the age-paired control group (p < 0.001). The ratio of AMH/follicle density was 1:1 (1.8/1.8) in women with DOR and 2:1 (14.4/7.0) in the age-paired controls. Analyses for gonadotropin receptor polymorphisms could not explain the characteristics of women with DOR. The proportion of secondary follicles was higher in women with DOR compared with controls (4.6% versus 1.4%, p = 0.0003). Pooling all patients, the follicle density decreased significantly by 7.7% for every year added (p < 0.0001). The women with DOR had lower follicle densities than the controls, but the slopes were equal in the two cohorts. CONCLUSIONS: Follicle density and AMH concentrations correlate also when AMH is low. However, AMH is only a reliable marker for the true ovarian reserve when age is included in the estimation and women with DOR may have more follicles than their AMH levels imply.
PURPOSE: To evaluate the association between anti-Müllerian hormone (AMH) and follicle density in infertile women with diminished ovarian reserve (DOR) versus women with normal ovarian reserve? METHODS: Case-control study comparing follicle densities in ovarian cortex from 20 infertile women with DOR (AMH ≤ 5 pmol/L) and 100 controls with presumed normal ovarian reserve. RESULTS: For all women > 25 years, the follicle densities correlated positively with AMH levels. For each single picomole per liter increase in AMH the follicle density increased by 6% (95% CI 3.3-8.5%) when adjusted for age. This was similar for women with DOR and controls. The follicle density was 1.8 follicles/mm3 cortical tissue in women with DOR versus 7.0 in age-paired controls (p = 0.04). The women with DOR had a median AMH of 1.8 pmol/L versus 14.4 pmol/L in the age-paired control group (p < 0.001). The ratio of AMH/follicle density was 1:1 (1.8/1.8) in women with DOR and 2:1 (14.4/7.0) in the age-paired controls. Analyses for gonadotropin receptor polymorphisms could not explain the characteristics of women with DOR. The proportion of secondary follicles was higher in women with DOR compared with controls (4.6% versus 1.4%, p = 0.0003). Pooling all patients, the follicle density decreased significantly by 7.7% for every year added (p < 0.0001). The women with DOR had lower follicle densities than the controls, but the slopes were equal in the two cohorts. CONCLUSIONS: Follicle density and AMH concentrations correlate also when AMH is low. However, AMH is only a reliable marker for the true ovarian reserve when age is included in the estimation and women with DOR may have more follicles than their AMH levels imply.