Effect of Intervention on Progesterone Levels Before Euploid Embryo Transfer in Pregnancy Outcomes.

Transferring an euploid embryo avoids one of the main reasons of miscarriage and implantation failure (1), overcoming confounding factors such as embryo ploidy or maternal age. Frozen Euploid Embryo Transfer (FEET) is routinely performed under standard hormone replacement therapy (HRT) and could be considered the best model for evaluating the impact of the endometrial preparation in clinical pregnancy rate and also in miscarriage rate.

Recently several authors have paid attention to serum progesterone (P) as a possible factor influencing Frozen Embryo Transfer (FET) outcomes. P plays an important role in endometrial gland formation, embryonic implantation and pregnancy maintenance. Labarta et al. (2) described in blastocyst FET performed under HRT that serum P <9.2 ng/mL measured on the transfer day is associated to significantly lower ongoing pregnancy rate (OR 0.297, 95% CI:0.113-0.779).

Recently the investigators have analyzed 244 FEET performed under HRT in a retrospective study (3). Preimplantation genetic testing for aneuploidies (PGT-A) was carried out as previously described (4). Embryos that reached the blastocyst stage were biopsied and frozen immediately afterwards using the vitrification method (5). Euploid embryos were transferred in a subsequent cycle under HRT. Serum P was analyzed the day previous to FEET. Patients with serum P <10.6 ng/mL had significantly higher miscarriage rate (26.6% vs 9.5%, p=0.007) and lower live birth rate (47.5% vs 62.3 %, p= 0.029) than those with serum P >10.6 ng/mL. The investigators also observed that patients with serum P >13.1 ng/mL had the lowest miscarriage rate (9.1%) and the highest live birth rate (65.6%). The worst outcomes were observed when serum P was <8.06 ng /mL (41% live birth rate and 32.4% miscarriage rate).

As miscarriage was higher among FEET cycles with serum P <10.6 ng/ml, the investigators hypothesize that altering the progesterone supplementation scheme could potentially reduce miscarriage rates and increase live birth rate. The purpose of this study is to modify the standard progesterone supplementation in FEET under HRT (vaginal micronized progesterone 200 mg every 8 hours) (6) according to serum P measured not only on the day prior to transfer but also on Beta subunit of Human Chorionic Gonadotropin (β-hCG) analysis day, and to probe if this intervention reduces miscarriage rate and increases pregnancy outcome.