Luteal Support in Frozen-Thawed Embryo Transfer Cycles

Sponsor

Centrum Clinic IVF Center (Other)

Overall Status

Completed

CT.gov ID

NCT03948022

Collaborator

(none)

151

Enrollment

Location

Arms

5.7

Actual Duration (Months)

26.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the clinical efficacy of 3 different luteal phase support in patients undergoing frozen-thawed embryo transfer cycles. Endometrium preparation will be hormone replacement in all cycles. Starting from day 11, group 1 will receive 100 mg micronized progesterone parenteral daily injections, group 2 will receive 90 mg bioadhesive gel vaginal twice daily and group 3 will receive 40 mg oral dydrogesterone daily tablets.

Condition or Disease	Intervention/Treatment	Phase
Implantation; Placenta Pregnancy Loss Frozen Embryo Luteal Support Luteal Phase Defect Assisted Reproduction	Drug: Dydrogesterone 10Mg Tablet (duphaston) Drug: Progesterone 50Mg/mL Oil Drug: Crinone 8% Vaginal Gel	Phase 4

Detailed Description

In natural pregnancy, successful implantation and pregnancy necessitates well-functioning corpus luteum. Luteal phase support (LPS) is critical in assisted conception cycles particularly for replacement frozen embryo transfer cycles owing to lack of corpus luteum. 3 different LPS options have been suggested:

Progesterone in oil (intramuscular injections) is rapidly absorbed after i.m. injection and high progesterone plasma concentrations are reached after approximately 2h. Despite satisfactory plasma levels, the possible side-effects of pain and swelling are limiting the use.
Vaginal application of progesterone is widely accepted with satisfactory endometrial levels and patient convenience. However, increased vaginal discharge and possible vaginal irritation are the most common side effects.
Oral administration of synthetic progesterone (dydrogesterone) would offer a convenient way of progesterone administration. Better bioavailability than natural progesterone and less cost makes dydrogesterone preferable. Also, good quality evidence revealed satisfactory outcomes in fresh embryo transfer cycles. However, there is lack of good quality evidence for dydrogesterone as a LPS in frozen-thawed cycles.

The investigator's aim is to compare 3 widely used LPS in frozen-thawed embryo transfer cycles.

Following allocation of the subjects, hormone replacement will be scheduled for the endometrial preparation. Briefly; On day 2 of menstrual bleeding, endometrial preparation with oral estradiol (E2) (2 mg twice daily) will be initiated. Approximately 10 days after initiation of E2 administration, the subject will undergo a transvaginal ultrasound examination to assess endometrial development and serum progesterone (P) level will be checked. Once the subject achieved a trilaminar endometrium with a thickness of >7 mm with serum P levels <1.5 ng/ml, she will start the progesterone treatment to which she will be randomized to one of the 3 arms. After 3 days of P treatment along with E2 pills, cleavage embryo transfer will be performed. If the subject will receive blastocyst, 5 days of P treatment will be scheduled.

If these criteria were not met at the first evaluation, she will allowed up to 10 additional days (20 days total) of estrogen stimulation.

Study Design

Study Type:

Interventional

Actual Enrollment :

151 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Which Luteal Support in Frozen-Thawed Embryo Transfer Cycles: A Randomized Controlled Trial

Actual Study Start Date :

Jun 30, 2021

Actual Primary Completion Date :

Dec 18, 2021

Actual Study Completion Date :

Dec 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: intramuscular progesterone progestan (progesterone) 50 mg/ml ampoules, 2 ampoules (100 mg) intramuscular starting from day 11 of the endometrial preparation cycle.	Drug: Progesterone 50Mg/mL Oil 100 mg daily intramuscular injections
Active Comparator: vaginal progesterone crinone %8 bioadhesive gel (progesterone) 90 mg, twice daily (180 mg/day) starting from day 11 of the endometrial preparation cycle.	Drug: Crinone 8% Vaginal Gel 180 mg daily vaginal gels
Experimental: oral dydrogesterone oral dydrogesterone (progesterone) 10 mg tablets, 2x2 (40 mg total)	Drug: Dydrogesterone 10Mg Tablet (duphaston) 40 mg daily oral tablets

Arm

Intervention/Treatment

Active Comparator: intramuscular progesterone

progestan (progesterone) 50 mg/ml ampoules, 2 ampoules (100 mg) intramuscular starting from day 11 of the endometrial preparation cycle.

Drug: Progesterone 50Mg/mL Oil

100 mg daily intramuscular injections

Active Comparator: vaginal progesterone

crinone %8 bioadhesive gel (progesterone) 90 mg, twice daily (180 mg/day) starting from day 11 of the endometrial preparation cycle.

Drug: Crinone 8% Vaginal Gel

180 mg daily vaginal gels

Experimental: oral dydrogesterone

oral dydrogesterone (progesterone) 10 mg tablets, 2x2 (40 mg total)

Drug: Dydrogesterone 10Mg Tablet (duphaston)

40 mg daily oral tablets

Outcome Measures

Primary Outcome Measures

ongoing pregnancy rate [12th week of pregnancy]
fetal cardiac activity beyond 12th week of gestation

Secondary Outcome Measures

clinical pregnancy rate [6th week of pregnancy]
fetal cardiac activity
abortion rate [during first 10 weeks of gestation]
miscarriage of the pregnancy pregnancy recently confirmed with positive beta hCG blood test

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

woman aged 20-40 years
Having available blastocyst(s) cryopreserved by vitrification method.

Exclusion Criteria:

requirement for fresh embryo(s);
presence of any clinically relevant systemic disease contraindicated for assisted reproduction or pregnancy
history of more than three failed cycles of IVF
history of recurrent abortions
allergy history for relevant drugs
body mass index of <18 or >38 kg/m2 at screening
current breastfeeding or pregnancy
refusal or inability to comply with the requirements of the protocol for any reason, including scheduled clinic visits and laboratory tests
trophectoderm or blastomere biopsy of the blastocyst(s) to be transferred