Progesterone Supplementation on Women Having Low Progesterone Levels on Transfer Day

NCT ID: NCT04897269

Last Updated: 2023-12-11

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

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

824 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-20

Study Completion Date

2024-06-20

Brief Summary

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The main objective of this study is to compare clinical pregnancy rates between two groups of women who have progesterone levels below 10 ng/mL on the day of frozen embryo transfer: group 1 (vaginal micronized progesterone supplemented with progesterone intramuscular 50 mg per day) and group 2 (vaginal micronized progesterone with no supplementation)

Detailed Description

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Trial Design:

Single center, longitudinal, randomized, interventional, controlled, pharmacological study, enrolling women attending clinical Centers of medically assisted reproduction (ART).

The study protocol consists in the record of all the diagnostic and clinical outcome parameters, according to clinical practice, for the following patient cohorts:

* The patients who are undergoing frozen embryo transfers with blastocyst or cleavage stage embryos and have progesterone levels below 10 ng/mL on the day of embryo transfer
* Study groups

* Group supplemented with progesterone intramuscular 50 mg per day until the day of beta-hcg testing (Intervention group);
* Group with no supplementation (Control group).

* Endometrial cycle is started with estradiol valerate dose of 4 mg to 8 mg per day, the patients then are appointed to have ultrasound scan of their endometrium every 3 to 7 days and the dose of estradiol may be increased to 16 mg per day maximum depends on the thickness of endometrium; when their endometrium reach 8 mm or higher and duration of endometrial preparation is ≥ 12 days, the embryo transfer will be planned and transvaginal progesterone are prescribed according to the day of transfer.
* If this is the first cycle of embryo transfer and she is \< 35 years of age, 1 grade 1 embryo is transferred, otherwise 2 embryos are transferred.
* In the morning of embryo-transferred day, all patients will have their blood tested for progesterone levels, if their levels below 10 ng/mL, they will be recruited into the study and randomized into two groups.
* In the study group, the patients will be prescribed with intramuscular progesterone supplemetation 50 mg + 800mg vaginal micronized progesterone per day for 14 days, until the day of beta-hcg testing.
* In the control group, the patients will continue their regular medications (800mg vaginal micronized progesterone per day) until the day of beta-hcg testing without any progesterone supplementation.
* If the beta-hcg test is positive, the patients will be continued their prescriptions depending on study or control group as mentioned above till 7 weeks of pregnancy when the fetal heart can be confirmed, then the patients will be followed up till 11 - 12 weeks of pregnancy

Conditions

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Assisted Reproductive Technology

Keywords

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low progesterone levels progesterone supplementation clinical pregnancy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients who have progesterone levels below 10 ng/mL on the day of embryo transfer will be randomized into 2 groups:

1. Those who will be supplemented with intramuscular progesterone 50mg per day till day of beta-hcg testing
2. Those who will continue their regular medications
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Control group

In the control group, the patients will be indicated with standard protocol, micronized progesterone (Cyclogest pessary) 400mg two times per day for 14 days, without any progesterone supplementation. If the beta-hcg test is positive, the patients will be treated with the same protocol and followed till 7 weeks of pregnancy when the fetal heart can be confirmed

Group Type NO_INTERVENTION

No interventions assigned to this group

Study group

In the interventional group,the patients will be indicated with standard protocol, micronized progesterone (Cyclogest pessary) 400mg x 2 per day for 14 days, supplemented with intramuscular progesterone (Progesterone 25mg/ml) 25 mg x 2 at one time per day for 14 days. If the beta-hcg test is positive, the patients will be treated with the same protocol and followed till 7 weeks of pregnancy when the fetal heart can be confirmed

Group Type EXPERIMENTAL

Progesterone supplementation

Intervention Type PROCEDURE

This procedure is to add more progesterone on those who have low progesterone levels on the day of embryo transfer

Interventions

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Progesterone supplementation

This procedure is to add more progesterone on those who have low progesterone levels on the day of embryo transfer

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients undergone ART with frozen embryo transfer, blastocyst or cleavaged stage embryo transfer, from 18-45 years of age
* Normal BMI
* HRT for Endometrial preparation in FET cycles

Exclusion Criteria

* Oocyte donor cycles
* Surrogacy
* IVM
* PGT
* Abnormal Uterine (firbroids 0 -\> 3 according to FIGO classification, polyp, adenomyosis, congenital malformation)
* Uterus fibroids type 4,5 (Figo classification) \> 4cm
* History of recurrent implantation failure
* Endometrial thickness \<7mm on the day of ET
* Cesarean scar defect (isthmocele)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Tu Du Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Le Thi Minh Chau

MD, MMSc, PhD, Head of Infertility department of Tu Du hospital

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chau TM Le

Role: PRINCIPAL_INVESTIGATOR

Department of Infertility, Tu Du Hospital

Locations

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Department of Infertility of Tu Du hospital

Ho Chi Minh City, , Vietnam

Site Status RECRUITING

Countries

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Vietnam

Central Contacts

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Chau TM Le, PhD

Role: CONTACT

Phone: +84908429006

Email: [email protected]

Anh Q Nguyen, Master

Role: CONTACT

Phone: +84976137562

Email: [email protected]

Facility Contacts

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Chau TM Le, PhD

Role: primary

Anh Q Nguyen, MMSc

Role: backup

References

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Cedrin-Durnerin I, Isnard T, Mahdjoub S, Sonigo C, Seroka A, Comtet M, Herbemont C, Sifer C, Grynberg M. Serum progesterone concentration and live birth rate in frozen-thawed embryo transfers with hormonally prepared endometrium. Reprod Biomed Online. 2019 Mar;38(3):472-480. doi: 10.1016/j.rbmo.2018.11.026. Epub 2019 Jan 5.

Reference Type RESULT
PMID: 30642638 (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 RESULT
PMID: 30585507 (View on PubMed)

Labarta E, Mariani G, Holtmann N, Celada P, Remohi J, Bosch E. 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. 2017 Dec 1;32(12):2437-2442. doi: 10.1093/humrep/dex316.

Reference Type RESULT
PMID: 29040638 (View on PubMed)

Volovsky M, Pakes C, Rozen G, Polyakov A. Do serum progesterone levels on day of embryo transfer influence pregnancy outcomes in artificial frozen-thaw cycles? J Assist Reprod Genet. 2020 May;37(5):1129-1135. doi: 10.1007/s10815-020-01713-w. Epub 2020 Feb 10.

Reference Type RESULT
PMID: 32043182 (View on PubMed)

Le TMC, Duong KT, Nguyen QA, Ong PT, Nguyen THN, Thai TCT, Le QT, Roque M, Alviggi C. Effectiveness of progesterone supplementation in women presenting low progesterone levels on the day of frozen embryo transfer: a randomised controlled trial. BMJ Open. 2022 Feb 23;12(2):e057353. doi: 10.1136/bmjopen-2021-057353.

Reference Type DERIVED
PMID: 35197354 (View on PubMed)

Other Identifiers

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656/BVTD-HDDD

Identifier Type: -

Identifier Source: org_study_id