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

NCT ID: NCT03740568

Last Updated: 2020-07-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

598 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-15

Study Completion Date

2020-02-28

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Normal Progesterone group

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

Group Type OTHER

Normal Progesterone

Intervention Type 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

Low Progesterone group

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

Group Type EXPERIMENTAL

Low Progesterone

Intervention Type 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

Interventions

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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

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fundación Santiago Dexeus Font

OTHER

Sponsor Role collaborator

Dexeus Clinic Woman

OTHER

Sponsor Role collaborator

Fundacion Dexeus

OTHER

Sponsor Role lead

Responsible Party

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Buenaventura Coroleu

Head Reproductive Service

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bueaventura Coroleu, PhD

Role: STUDY_CHAIR

Hospital Universitari Dexeus. Departamento de Ginecología, Obstetricia y Reproducción

Locations

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Departamento Ginecología, Obstetricia y Reproducción . Hospital Universitari Dexeus

Barcelona, , Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 28433371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29177428 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30585507 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29798732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23744895 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16632462 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33686413 (View on PubMed)

Related Links

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Other Identifiers

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FSD-PRG-2018-09

Identifier Type: -

Identifier Source: org_study_id

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