Progesterone Supplementation on Women Having Low Progesterone Levels on Transfer Day

Assisted Reproductive Technology Clinical Trial

Official title:

Effectiveness of Progesterone Supplementation for Women Having Low Progesterone Levels on the Day of Frozen Embryo Transfer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04897269
• Other study ID #: 656/BVTD-HDDD
• Status: Recruiting
• Phase: Phase 3
• Start date: May 20, 2021
• Est. completion date: June 20, 2024

Study information

• Verified date: December 2023
• Source: Tu Du Hospital
• Contact: Chau TM Le, PhD
• Phone: +84908429006
• Email: dr.lethiminhchau[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 824
• Est. completion date: June 20, 2024
• Est. primary completion date: May 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Assisted Reproductive Technology

Intervention

Procedure:
• Progesterone supplementation
This procedure is to add more progesterone on those who have low progesterone levels on the day of embryo transfer

Locations

Country	Name	City	State
Vietnam	Department of Infertility of Tu Du hospital	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
Tu Du Hospital

Country where clinical trial is conducted

Vietnam, 

References & Publications (4)

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. 201 — View Citation

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 — View Citation

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 st — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy rate	defined as the pregnancy completed 11 - 14 weeks of gestation and having vital fetus	week 11 - 14 of pregnancy
Secondary	implantation rate	the percentage of embryos which successfully undergo implantation compared to the number of embryos transferred in a given period	3 weeks after embryo transfer
Secondary	Pregnancy rate	beta-hCG test is positive	2 weeks after embryo transfer
Secondary	clinical pregnancy rate	pregnancy when fetal heart can be confirmed	3 weeks after embryo transfer