The Young Low Responder and Polyglandular Autoimmunity

Abstract

Objectives: Recruitment and stimulation of a healthy cohort of oocytes remains the single most significant factor in the success of non-donor assisted reproduction (ART). Although an age-dependent decrease in ovarian reserve and fecundity is physiologic in women >40, the younger asymptotic low responder (LR) presents significant endocrine and ethical dilemmas concerning stimulation protocols and the ultimate decision to pursue donor oocytes.Design: Prospective evaluation of women demonstrating a low response to controlled ovarian hyperstimulation.Materials and Methods: 50 healthy, euthyroid, eumenorrheic women without endometriosis, previous surgery or significant family history, who were stimulated by ≥3 ampules of menotropins (HMG) produced ≤3 follicles. A control group of 18 similar euthyroid, eumenorrheic women with secondary infertility and normal HMG response served as the control group. 10 women with known premature ovarian failure were also included. All underwent evaluation of basal follicle stimulation hormone (FSH), thyroid stimulating hormone (TSH), thyroid antibody, antinuclear antibody (ANA) and sonographic assessment of mean pre-HMG ovarian diameter. ∗Results:AgeBasal FSHMean ovarian diameterHMG follicles+Thyroid antibodyControl33.75.830.17.427%LR<3934.68.3∗Significant differences P<0.05 control.24.1∗Significant differences P<0.05 control.2.2∗Significant differences P<0.05 control.68%∗Significant differences P<0.05 control.LR>3943.111.2∗Significant differences P<0.05 control.20.8∗Significant differences P<0.05 control.1.8∗Significant differences P<0.05 control.22%POF35.198.4∗Significant differences P<0.05 control.18.7∗Significant differences P<0.05 control.—44%∗ Significant differences P<0.05 control. Open table in a new tab Conclusions: The results of this study suggest: 1) The vast majority of unsuspected eumenorrheic LR demonstrates significantly decreased ovarian mass, similar to premature ovarian failure. 2) LR>39 years are most likely physiologic LR due to variabilities in decremental ovarian reserve. 3) LR<39 years demonstrates decreased ovarian mass, and a significant incidence of asymptomatic thyroid auto-antibody consistent with incipient polyglandular autoimmune disease. 4) The finding of ovarian diameters <25 mm and thyroid antibodies in young, eumenorrheic women suggests a poor prognosis for any fertility therapy and early counseling for donor oocytes as well as surveillance for autoimmune polyglandular sequelae. Objectives: Recruitment and stimulation of a healthy cohort of oocytes remains the single most significant factor in the success of non-donor assisted reproduction (ART). Although an age-dependent decrease in ovarian reserve and fecundity is physiologic in women >40, the younger asymptotic low responder (LR) presents significant endocrine and ethical dilemmas concerning stimulation protocols and the ultimate decision to pursue donor oocytes. Design: Prospective evaluation of women demonstrating a low response to controlled ovarian hyperstimulation. Materials and Methods: 50 healthy, euthyroid, eumenorrheic women without endometriosis, previous surgery or significant family history, who were stimulated by ≥3 ampules of menotropins (HMG) produced ≤3 follicles. A control group of 18 similar euthyroid, eumenorrheic women with secondary infertility and normal HMG response served as the control group. 10 women with known premature ovarian failure were also included. All underwent evaluation of basal follicle stimulation hormone (FSH), thyroid stimulating hormone (TSH), thyroid antibody, antinuclear antibody (ANA) and sonographic assessment of mean pre-HMG ovarian diameter. ∗Results:AgeBasal FSHMean ovarian diameterHMG follicles+Thyroid antibodyControl33.75.830.17.427%LR<3934.68.3∗Significant differences P<0.05 control.24.1∗Significant differences P<0.05 control.2.2∗Significant differences P<0.05 control.68%∗Significant differences P<0.05 control.LR>3943.111.2∗Significant differences P<0.05 control.20.8∗Significant differences P<0.05 control.1.8∗Significant differences P<0.05 control.22%POF35.198.4∗Significant differences P<0.05 control.18.7∗Significant differences P<0.05 control.—44%∗ Significant differences P<0.05 control. Open table in a new tab Conclusions: The results of this study suggest: 1) The vast majority of unsuspected eumenorrheic LR demonstrates significantly decreased ovarian mass, similar to premature ovarian failure. 2) LR>39 years are most likely physiologic LR due to variabilities in decremental ovarian reserve. 3) LR<39 years demonstrates decreased ovarian mass, and a significant incidence of asymptomatic thyroid auto-antibody consistent with incipient polyglandular autoimmune disease. 4) The finding of ovarian diameters <25 mm and thyroid antibodies in young, eumenorrheic women suggests a poor prognosis for any fertility therapy and early counseling for donor oocytes as well as surveillance for autoimmune polyglandular sequelae.