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

NCT03740568 | Completed

• 1 other identifier: FSD-PRG-2018-09
• Study Type: interventional
• Target: 598
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility; Progesterone; Frozen Embryo Transfer; Euploid Embryo Transfer; Pregnancy Outcome; Artificial Cycle; Ongoing Pregnancy

Outcome Measures

Primary Outcomes (3)

• Ongoing Pregnancy Rate (OPR)

  Ongoing Pregnancy Rate (OPR) beyond pregnancy week 12 in FEET according to serum P level and interventions on D4 and D5

  12 weeks after transfer procedure

• Miscarriage Rate (MR)

  Miscarriage Rate (MR) in FEET according to serum P level and interventions on D4 and D5.

  12 weeks after transfer procedure

• Concentration of serum P level

  P level

  D4, D5 and D14 of P supplementation

Secondary Outcomes (4)

• Rate of cancellation due to lack of response in case of additional Psc dose on D4.

  Day 5 of progesterone supplementation

• Rate of rescued cycles in case of additional Psc dose

  Day 5 of progesterone supplementation

• Ongoing Pregnancy Rate and Live Birth Rate according to serum P level and interventions n D14

  On day 14 of progesterone supplementation

• Live birth Rate (LBR)

  40 weeks after transfer procedure

Study Arms (2)

Normal Progesterone group

OTHER

Progesterone level \>10.64 ng/mL on day 4 of progesterone supplementation

Drug: Normal Progesterone

Low Progesterone group

EXPERIMENTAL

Progesterone level \<10.64 ng/mL on day 4 of progesterone supplementation

Drug: Low Progesterone

Interventions

Low Progesterone DRUG

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

Low Progesterone group

Normal Progesterone DRUG

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

Normal Progesterone group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Fundacion Dexeus: lead
• Fundación Santiago Dexeus Font: collaborator
• Dexeus Clinic Woman: collaborator

Study Sites (1)

Departamento Ginecología, Obstetricia y Reproducción . Hospital Universitari Dexeus

Barcelona, 08028, Spain

Location

Related Publications (7)

• Rubio C, Bellver J, Rodrigo L, Castillon G, Guillen A, Vidal C, Giles J, Ferrando M, Cabanillas S, Remohi J, Pellicer A, Simon C. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017 May;107(5):1122-1129. doi: 10.1016/j.fertnstert.2017.03.011. Epub 2017 Apr 19.

  PMID: 28433371 BACKGROUND

• Labarta E, Mariani G, Holtmann N, Celada P, Remohi J, Bosch E. Corrigendum: Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2018 Jan 1;33(1):178. doi: 10.1093/humrep/dex353. No abstract available.

  PMID: 29177428 BACKGROUND

• Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Alvarez M, Parriego M, Barri PN, Polyzos N, Coroleu B. Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates. Gynecol Endocrinol. 2019 May;35(5):439-442. doi: 10.1080/09513590.2018.1534952. Epub 2018 Dec 26.

  PMID: 30585507 BACKGROUND

• Coll L, Parriego M, Boada M, Devesa M, Arroyo G, Rodriguez I, Coroleu B, Vidal F, Veiga A. Transition from blastomere to trophectoderm biopsy: comparing two preimplantation genetic testing for aneuploidies strategies. Zygote. 2018 Jun;26(3):191-198. doi: 10.1017/S0967199418000084. Epub 2018 May 25.

  PMID: 29798732 BACKGROUND

• Sole M, Santalo J, Boada M, Clua E, Rodriguez I, Martinez F, Coroleu B, Barri PN, Veiga A. How does vitrification affect oocyte viability in oocyte donation cycles? A prospective study to compare outcomes achieved with fresh versus vitrified sibling oocytes. Hum Reprod. 2013 Aug;28(8):2087-92. doi: 10.1093/humrep/det242. Epub 2013 Jun 5.

  PMID: 23744895 BACKGROUND

• Martinez F, Boada M, Coroleu B, Clua E, Parera N, Rodriguez I, Barri PN. A prospective trial comparing oocyte donor ovarian response and recipient pregnancy rates between suppression with gonadotrophin-releasing hormone agonist (GnRHa) alone and dual suppression with a contraceptive vaginal ring and GnRH. Hum Reprod. 2006 Aug;21(8):2121-5. doi: 10.1093/humrep/del121. Epub 2006 Apr 21.

  PMID: 16632462 BACKGROUND

• Alvarez M, Gaggiotti-Marre S, Martinez F, Coll L, Garcia S, Gonzalez-Foruria I, Rodriguez I, Parriego M, Polyzos NP, Coroleu B. Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study. Hum Reprod. 2021 May 17;36(6):1552-1560. doi: 10.1093/humrep/deab031.

  PMID: 33686413 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Bueaventura Coroleu, PhD

  Hospital Universitari Dexeus. Departamento de Ginecología, Obstetricia y Reproducción

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Reproductive Service

Study Record Dates

• First Submitted: November 9, 2018
• First Posted: November 14, 2018
• Study Start: November 15, 2018
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2020
• Last Updated: July 29, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)