Luteal Support in Frozen-Thawed Embryo Transfer Cycles

Pregnancy Loss Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03948022
• Other study ID #: centrumtupbebek
• Status: Completed
• Phase: Phase 4
• Start date: June 30, 2021
• Est. completion date: December 20, 2021

Study information

• Verified date: December 2021
• Source: Centrum Clinic IVF Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: December 20, 2021
• Est. primary completion date: December 18, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Assisted Reproduction
• Implantation; Placenta
• Luteal Phase Defect
• Luteal Support
• Pregnancy Loss

Intervention

Drug:
• Dydrogesterone 10Mg Tablet (duphaston)
40 mg daily oral tablets
• Progesterone 50Mg/mL Oil
100 mg daily intramuscular injections
• Crinone 8% Vaginal Gel
180 mg daily vaginal gels

Locations

Country	Name	City	State
Turkey	Ufuk University School of Medicine	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Centrum Clinic IVF Center

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

Devine K, Richter KS, Widra EA, McKeeby JL. Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomiz — View Citation

Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Repr — View Citation

Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M. Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial. Arch Gynecol Obstet. 2017 Jan;295(1):239-246. doi: 10.1007/s00404 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ongoing pregnancy rate	fetal cardiac activity beyond 12th week of gestation	12th week of pregnancy
Secondary	clinical pregnancy rate	fetal cardiac activity	6th week of pregnancy
Secondary	abortion rate	miscarriage of the pregnancy pregnancy recently confirmed with positive beta hCG blood test	during first 10 weeks of gestation