The Importance of Embryo Transfer Day Progesterone Value in Natural Cycle Frozen Embryo Transfers and the Evaluation of the Effect of Rescue Therapy on Pregnancy Outcomes in Patients With Low Progesterone Levels

Infertility Clinical Trial

Official title:

The Importance of Embryo Transfer Day Progesterone Value in Natural Cycle Frozen Embryo Transfers and the Evaluation of the Effect of Rescue Therapy on Pregnancy Outcomes in Patients With Low Progesterone Levels: A Multicentric Randomized Controlled Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05481684
• Other study ID #: 26.07.2022-E.71262
• Status: Recruiting
• Phase: N/A
• Start date: August 8, 2022
• Est. completion date: December 1, 2023

Study information

• Verified date: August 2023
• Source: Bezmialem Vakif University
• Contact: pinar özcan, PhD
• Phone: +905414031625
• Email: pinarozcan[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Thanks to recent advances in clinical practice and laboratory, embryo cryopreservation has become the first-line procedure in assisted reproductive technology. Improved laboratory techniques have increased the number of available embryos derived from an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle. Implementation of a single embryo transfer policy to improve vitrification, improve postwarm embryo survival rates, and reduce multiple pregnancies without reducing cumulative birth rates has contributed to an increase in the number of frozen-warms (1,2) Embryo freezing; It is becoming an adopted practice for an increasing number of indications, including prevention of ovarian hyperstimulation syndrome, preimplantation genetic testing (PGT), late follicular phase progesterone elevation, and embryo-endometrial asynchrony. In our study, we are investigating the effect of pre-transfer serum progesterone levels on pregnancy outcomes in patients who underwent frozen-thawed embryo transfer.Supplementary progesterone preparations can be used to prevent luteal phase defect and to provide progesterone support in cycle preparations for frozen-thawed embryo transfer(3). The aim in this study is to show the effect of serum progesterone level on the pregnancy results on the day of embryo transfer in natural cycles.

Description:

The patients to be included in the study are the patients followed in the IVF centers of two different hospitals.Patients between the ages of 20-42 and having a BMI of <30, who are scheduled for IVF due to tubal factor, infertility of unknown cause, mild male factor, and anovulation will be included in the study. An antagonist (Cetrotide; Serono, Geneva, Switzerland) protocol will be used for controlled ovarian hyperstimulation, and recombinant follicle-stimulating hormone (recFSH) (Gonal F; Serono, Geneva, Switzerland) and Human Menopausal Gonadotropin (HMG) (Merional; Switzerland) will be used for stimulation. The dose of gonadotropin to be administered to patients is in the range of 150 to 450 IU per day and will be determined according to the age of each patient, serum FSH and E2 levels in the early follicular phase, and the number of antral follicles determined by ultrasound in the early follicular phase. Adjustment of the gonadotropin dose during the treatment will be adjusted by serial ultrasound measurements of the follicle diameters developed during the treatment and serum E2 levels. The patient's eggs will be collected at 34-36 hours. Fertilization check will be done the next day. During 3-5 days of embryo culture, embryo quality will be determined according to the D.Gardner criteria (1999). Embryos will be frozen on the 3rd or 5th day and transferred to a planned frozen cycle within the next month. In the frozen cycle, basal ultrasonography is performed on the 3rd day of the menstrual cycle and if there is no follicle over 10 mm, the patient will be called for a control on the 10th day of the cycle if the endometrial thickness is less than 5 mm. In the follow-ups after the 10th day, daily LH monitoring will be performed with the dominant follicle reaching 15 m in diameter. When the LH level increases 1.8 times, it will be considered as LH surge. Serum progesterone level will be checked on embrio transfer day. The patients with serum progesterone value below 10 on the day of embryo transfer will be divided into two groups, and the first group will be given vaginal progesterone (Lutinus 2*1) as rescue therapy, and the second group will be given subcutaneous progesterone (prolutex 1*1) as rescue therapy. Rescue treatment will not be applied to those whose serum progesterone level is 10 and above on the ET day. At the time of presumed LH surge, E2 (estradiol), P4 (progesterone), LH will be checked and the endometrial thickness in the uterus will be measured.

If the patient's endometrium is suitable, embryo transfer will be performed and a blood pregnancy test will be performed 10-12 days later. The research is planned to last for a year, starting in August 2022 and ending in August 2023. Patient data will be evaluated as prospective data analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 42 Years

Eligibility

Inclusion Criteria:

• Women between the ages of 20-42 who applied to the infertility clinic

• BMI<30

Exclusion Criteria:

• Severe male factor (Sperm count <5 ml/ml, progressively motile sperm count <10%)

• Intrauterine structural anomalies not corrected by surgery

• Hydrosalpenx if not underwent surgery

• Refusal to participate in the study

• cycle cancelation

Related Conditions & MeSH terms

• Infertility
• IVF
• Progesterone

Intervention

Other:
• Normal Progesterone group
No progesterone supplementation
• Low Progesterone group
Progesterone level <10 ng/mL on ET day. If serum progesterone levels were <10 ng/ml at ET day, vaginal pills (Lutinus 2*1) or SC progesterone daily (Prolutex) was given to patients and ET was performed on the same day. Progesterone supplementation was discontinued if there was no pregnancy. Progesterone supplementation at the same dose was continued until 10 gestational weeks for viable pregnancies.

Locations

Country	Name	City	State
Turkey	Acibadem Atasehir Hospital	Istanbul
Turkey	Bezmialem Foundation University	Istanbul
Turkey	Novaart IVF and Women's Health Center	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Bezmialem Vakif University

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

Groenewoud ER, Cohlen BJ, Macklon NS. Programming the endometrium for deferred transfer of cryopreserved embryos: hormone replacement versus modified natural cycles. Fertil Steril. 2018 May;109(5):768-774. doi: 10.1016/j.fertnstert.2018.02.135. — View Citation

Loutradi KE, Kolibianakis EM, Venetis CA, Papanikolaou EG, Pados G, Bontis I, Tarlatzis BC. Cryopreservation of human embryos by vitrification or slow freezing: a systematic review and meta-analysis. Fertil Steril. 2008 Jul;90(1):186-93. doi: 10.1016/j.fe — View Citation

Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, Vanderpoel S, Racowsky C. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for t — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rates	fetal heartbeat by transvaginal ultrasound	average of 1 year
Secondary	Ongoing pregnancy rate	Pregnancies that continue until the 12th week of pregnancy	average of 15 month
Secondary	Miscarriage	any clinical pregnancy lost before pregnancy week 12	average of 15 month