Effect of Intervention on Progesterone Levels Before Euploid Embryo Transfer in Pregnancy Outcomes.
Condition: Infertility; Progesterone; Frozen Embryo Transfer; Euploid Embryo Transfer; Pregnancy Outcome; Artificial Cycle; Ongoing Pregnancy
MeSH terms: Infertility
Study type: Interventional

Summary: 
      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.
    


Intervention name(s): Low Progesterone; Normal Progesterone
Intervention type(s): Drug; Drug
Intervention description(s): Additional daily dosage of subcutaneous progesterone (Psc) 25 mg/day at night since D4 (vaginal micronized P 200mg/200mg/200mg + Psc 25 mg/night) New Progesterone analysis on D5 before warming the embryo. Group 2a (Canceled Group, P on D5 <10.64 ng/mL): cancel PGT-FET. Scheduling a new procedure under different P supplementation.
Group 2b (Restored Progesterone Group, P on D5 >10.64 ng/mL): continue HRT as previously described (vaginal micronized P 200mg/200mg/200mg + Psc 25 mg/night). Warming and transfer the same day (D5)
Beta-hCG and P analysis is performed on the 14th day of P supplementation (D14). In case of positive Beta-hCG analysis:
If P is >10.64 ng /mL: the same P supplementation is continued. If P is <10.64 ng /mL: an additional dosage of vaginal micronized P (200 mg) is added at night; Same Progesterone supplementation (vaginal micronized P 200mg/200mg/200mg) Warming and transfer on D5
Beta-hCG and P analysis is performed on the 14th day of P supplementation (D14). In case of positive Beta-hCG analysis:
If P is >10.64 ng /mL: the same P supplementation is continued. If P is <10.64 ng /mL: an additional dosage of vaginal micronized P (200 mg) is added at night
Intervention MeSH terms: Progesterone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment