Abstract
Study question
Do woman with diminished ovarian reserve exhibit poor blastocyst formation and ploidy outcomes, irrespective of age?
Summary answer
Patients with extreme diminished ovarian reserve (AMH≤0.65ng/ml) have a lower chance to have at least one euploid blastocyst compared to their age-related reference population (AMH=1.3–6.25ng/ml).
What is known already
AMH is an established marker of the ovarian reserve for predicting ovarian response to ovarian stimulation and it is strongly correlated with female age.
However, it has been suggested that AMH is not only a quantitative, but also a qualitative biomarker of oocyte/embryo competence. Previous studies show conflicting outcomes as to whether reduced ovarian reserve per se is associated with decreased oocyte developmental competence, leading to increased aneuploidy rates in embryos independent of the patient’s age.
Study design, size, duration
A retrospective analysis was performed between March 2017 and July 2020 at ART Fertility Clinics (Abu Dhabi) including all couples that were triggered for final oocyte maturation and planned for Preimplantation Genetic Testing for Aneuploidies (PGT-A). Patients were stratified into four age categories [≤30, 31–35, 36–40, >40 years]. For each age category patients were further divided into three AMH groups: ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml (reference group).
Participants/materials, setting, methods
Trophectoderm biopsy samples were subjected to Next Generation Sequencing. AMH serum levels (ng/ml) were determined using the commercial fully automated Elecsys® (Roche) assay. Patients with a Progesterone rise of > 1.5ng/ml on the day of final oocyte maturation and patients with AMH values >6.25ng/ml were excluded from the analysis. Per patient that was triggered, the chance to have at least one euploid blastocyst in that cycle, was calculated.
Main results and the role of chance
A total of 1.300 couples were included with an mean maternal age of 35.6±6.2 years, AMH of 2.1 ±1.5ng/ml and body mass index of 27.5±5.0 kg/m2. The chance to have at least one blastocyst biopsied per cycle was affected in all patients with extreme low AMH (≤0.65ng/ml), irrespective of age; ≤30 years: 58.33%–100.00%–94.84% (p < 0.001); 31–35 years: 50.00%–74.55%–95.32% (p < 0.001); 36–40 years: 56.52%–81.93%–92.56% (p < 0.001) and ≥40 years: 38.06%–73.02%–88.24% (p < 0.001), for AMH ≤0.65ng/ml, 0.65–1.3ng/ml and 1.31–6.25ng/ml, respectively. In all age categories, patients with AMH values ≤0.65ng/ml had a significantly reduced probability of having a euploid blastocyst compared to the reference group (1.31–6.25ng/ml). For women ≤30 years the chances of getting a euploid blastocyst decreased from 88.89% (n = 252) to 41.67% (n = 12) (OR 0.01 [0.03–0.30], p < 0.001), for 31–35 years from 88.09% (n = 235) to 43.75% (n = 32) (OR 0.10 [0.05–0.23], p < 0.001), for 36–40 years from 77.67% (n = 215) to 21.74% (n = 69) (OR 0.08 [0.04–0.15], p < 0.001) and among women >40 years from 29.42% (n = 102) to 6.45% (n = 155) (OR 0.16 [0.08–0–36], p < 0.001). Woman within AMH range of 0.65–1.3ng/ml presented the same decreased probability of having a euploid blastocyst only when 31–35 (52.73%, n = 55) or 36–40 years old (56.63%, n = 83) (OR 0.15 [0.08–0.29], p < 0.001 and OR 0.37 [0.22–0.64], p < 0.001, respectively).
Limitations, reasons for caution
The main limitation of this study is its retrospective design.
Wider implications of the findings: AMH is a clear biomarker of oocyte-embryo competence. Incorporation of AMH-specific counseling recommendations into clinical practice guidelines, could lead to a more informed guidance on cycle ploidy outcomes, rather than age alone.
Trial registration number
Not applicable
A 5-year analysis of demographics, cycle characteristics and reproductive outcomes of 907 egg freezing cycles in patients with diminished ovarian reserve and age-related fertility decline
