P-729: Are women with premature ovarian aging (POA) at increased risk for chromosomally abnormal embryos? The association between embryonic aneuploidy rates and POA

Abstract

The hallmarks of premature ovarian aging (POA) are abnormal ovarian baseline function tests and ovarian resistance to stimulation with gonadotropins at an unusually young age. Since those features are also observed in women with age-appropriate ovarian aging (AAOA), some authors have suggested that POA might only represent a leftward shift of the normal ovarian aging curve towards younger age. If this was, indeed, the case, women with POA should demonstrate increased aneuploidy rates in their embryos when compared with age matched controls with normal ovarian function. Retrospective cohort study We retrospectively identified 20 consecutive IVF cycles in women with POA, up to age 40 years, and matched those cycles with 20 control cycles in women, of identical ages, with normal ovarian function. POA was diagnosed if patients had a history of ovarian resistance, based on the production of inadequate oocyte numbers with age-appropriate ovarian stimulation and, therefore, required age-inappropriate, maximal ovarian stimulation, or if they required such stimulation based on elevated baseline FSH levels. Normal ovarian function was considered to be present if patients produced, with age-appropriate ovarian stimulation, normal age-appropriate oocyte numbers and showed normal baseline FSH levels. All POA patients received ovarian stimulation with a microdose agonist protocol, followed by 450-600 IU of goandotropins daily, while AAOA cycles were treated with long agonist protocols, followed by 225-300 IU of gonadotropins. POA and AAOA patients underwent preimplantation genetic diagnosis (PGD) by fluorescence in situ hybridization (FISH) for chromosomes X, Y, 13, 16, 18, 21, 22 on day-3 after fertilization, and transfer at blastocyst stage on day-5. Patients were represented by only one cycle and the statistical analysis was performed using SPSS for Windows. Standard version 10.0.7. Based on the sample size of the study a power of 82.1% was reached to detect a 60% difference. POA and AAOA patients did not differ statistically in age (mean, 34.6, range 27-40 years for both), oocyte numbers, embryo numbers transferred, quality of embryos transferred and initially positive pregnancy tests (43% vs 47%). Amongst a total of 258 embryos, the aneuploidy rate in POA cycles was 52.6% vs. 52.2% in AAOA patients. POA cycles demonstrated, however, significantly higher baseline FSH levels (p<0.04) and significantly higher medication dosages (p< 0.001). There was a strong trend towards lower ongoing pregnancy rates in POA patients which, however, failed to reach significance (21% vs 41%), an obvious result of higher clinical miscarriage rates (50% vs 13%). While the clinical presentation of POA, characterized by diminished ovarian reserve, decreased ongoing pregnancy rates, and increased miscarriage (especially after confirmed fetal heart), mimics the presentation of AAOA, the observation that POA is not characterized by increased aneuploidy rates, controlled for age, suggests that the pathophysiology of POA differs from that of AAOA. This study, therefore, provides convincing evidence that, other than routine chromosomal, abnormalities induce pregnancy loss in POA, and especially after positive fetal heart tones have been obtained. Non-chromosomal pregnancy loss may thus represent another characteristic clinical feature of POA and may shed light on the pathophysiology of POA.