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

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ClinicalTrials.gov Identifier: NCT03740568
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
Fundación Santiago Dexeus Font
Dexeus Clinic Woman
Information provided by (Responsible Party):
Buenaventura Coroleu, Institut Universitari Dexeus

Brief 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.


Condition or disease Intervention/treatment Phase
Infertility Progesterone Frozen Embryo Transfer Euploid Embryo Transfer Pregnancy Outcome Artificial Cycle Ongoing Pregnancy Drug: Low Progesterone Drug: Normal Progesterone Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 590 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Intervention on Progesterone Levels Before Euploid Embryo Transfer in Pregnancy Outcomes
Estimated Study Start Date : December 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Normal Progesterone group
Progesterone level >10.64 ng/mL on day 4 of progesterone supplementation
Drug: Normal Progesterone

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


Experimental: Low Progesterone group
Progesterone level <10.64 ng/mL on day 4 of progesterone supplementation
Drug: Low Progesterone

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





Primary Outcome Measures :
  1. Ongoing Pregnancy Rate (OPR) [ Time Frame: 12 weeks after transfer procedure ]
    Ongoing Pregnancy Rate (OPR) beyond pregnancy week 12 in FEET according to serum P level and interventions on D4 and D5

  2. Miscarriage Rate (MR) [ Time Frame: 12 weeks after transfer procedure ]
    Miscarriage Rate (MR) in FEET according to serum P level and interventions on D4 and D5.

  3. Concentration of serum P level [ Time Frame: D4, D5 and D14 of P supplementation ]
    P level


Secondary Outcome Measures :
  1. Rate of cancellation due to lack of response in case of additional Psc dose on D4. [ Time Frame: Day 5 of progesterone supplementation ]
  2. Rate of rescued cycles in case of additional Psc dose [ Time Frame: Day 5 of progesterone supplementation ]
  3. Ongoing Pregnancy Rate and Live Birth Rate according to serum P level and interventions n D14 [ Time Frame: On day 14 of progesterone supplementation ]
  4. Live birth Rate (LBR) [ Time Frame: 40 weeks after transfer procedure ]
    Live birth Rate (LBR) in FEET according to serum P level and interventions on D4 and D5 and D14.



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • FEET of at least one single embryo
  • HRT
  • Endometrial thickness >= 6 mm measured day 4 of progesterone supplementation

Exclusion Criteria:

  • Patients with mosaic embryos.
  • Uterine abnormality.
  • Natural cycle protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03740568


Contacts
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Contact: Ignacio Rodriguez, Bsc 0034932274700 ext 22029 nacrod@dexeus.com

Locations
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Spain
Departamento Ginecología, Obstetricia y Reproducción . Hospital Universitari Dexeus Recruiting
Barcelona, Spain, 08028
Contact: Manuel Alvarez, MD         
Sponsors and Collaborators
Institut Universitari Dexeus
Fundación Santiago Dexeus Font
Dexeus Clinic Woman
Investigators
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Study Chair: Bueaventura Coroleu, PhD Hospital Universitari Dexeus. Departamento de Ginecología, Obstetricia y Reproducción

Additional Information:
Publications:

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Responsible Party: Buenaventura Coroleu, Head Reproductive Service, Institut Universitari Dexeus
ClinicalTrials.gov Identifier: NCT03740568     History of Changes
Other Study ID Numbers: FSD-PRG-2018-09
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Infertility
Genital Diseases, Male
Genital Diseases, Female
Progesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs