Benefit of Amlodipine in HRT Cycle for Frozen Embryo Transfer in the Correction of Uterine Pulsatility Index

Embryo implantation depends on two main factors: embryo grading quality and endometrial receptivity.Numerous tools have been suggested to evaluate these two factors. Measurement of the pulsatility index (PI) of the uterine arteries is associated with extremely low chances of pregnancy when it is high, especially higher than 3. A pilot study of women with premature ovarian failure with at least one of the uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour. We are therefore interested in exploring this accessible, non-invasive and inexpensive tool, in the evaluation of endometrial receptivity before an embryo transfer.

Embryo implantation is a key stage that depends on two main factors: embryo grading quality and endometrial receptivity. Numerous tools have been suggested to evaluate these two factors, without making it possible to predict with certainty the outcome of an embryo transfer in terms of pregnancy. However, some diagnostic tests have shown a good negative predictive value: it is the case of the measurement of the pulsatility index (PI) of the uterine arteries which is associated with extremely low chances of pregnancy when it is high, especially higher than 3 (Cacciatore et al., 1996; Steer et al., 1992). The Pulsatility Index PI is calculated by the ratio between the maximum amplitude of the tracing and the mean velocity. It evolves according to downstream resistance. Uterine hypoperfusion would readily be associated with subfertility (Goswamy et al., 1988). The uterine arterial pulsatility index is easily accessible during pelvic ultrasound, with satisfactory intra- and inter-observer reproducibility (Steer et al., 1995). There is no significant difference between the measurement of the right and left uterine PI (Favre et al., 1993). Uterine PIs vary during the menstrual cycle (Goswamy and Steptoe, 1988) and depending on hormonal effects (de Ziegler et al., 1991; Strigini et al., 1995) or ovarian micropolycystic status (PCOS, syndrome of polycystic ovaries) of the patient (Resende et al., 2001). The impact of tobacco (Battaglia et al., 2011) and parity (Guedes-Martins et al., 2015) on uterine PIs is described in the literature. Age, although controversial, does not seem to have an impact on uterine PIs, at least in premenopausal women case (Check et al., 2000). Likewise, body mass index (BMI) could have an impact on PIs, as in increased PIs in obese women (Battaglia et al., 1996; Zeng et al., 2013) If high uterine PIs are associated with reduced chances of pregnancy, how can they be improved? A pilot study of women with premature ovarian failure with uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour (Huissoud et al., 2004). This medication could therefore be promising in the treatment of patients in assisted medical reproduction (ART) for whom the measurements of the uterine PIs would be greater than 3 and therefore have lower chances of pregnancy. This study aims to investigate weither the use of a calcium channel blocker (amlodipine) improves the value of uterine PIs in patients with at least one of the uterine PIs greater than 3, during a cycle for frozen embryo transfer (FET).