Clinical trial NCT05481684: 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
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
IVF
Progesterone
Lead sponsor: Bezmialem Vakif University
Sponsor class: OTHER
First posted: 2022-08-01
Enrollment: 126
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical pregnancy rates
timeFrame: average of 1 year
Secondary outcomes:
measure: Ongoing pregnancy rate
timeFrame: average of 15 month
measure: Miscarriage
timeFrame: average of 15 month
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Acıbadem Ataşehir Hospital
city: Istanbul
country: Turkey
facility: Bezmialem Foundation University
city: Istanbul
country: Turkey
facility: Novaart IVF and Women's Health Center
Study officials:
affiliation: Bezmialem Foundation University
name: pınar özcan, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Acıbadem Ataşehir Hospital
name: Cem Demirel, PhD
role: STUDY_CHAIR
affiliation: Novaart IVF and Women's Health Center
name: Mehmet Erdem, PhD
role: STUDY_CHAIR
References:
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 the development of global guidance. Hum Reprod Update. 2017 Mar 1;23(2):139-155. doi: 10.1093/humupd/dmw038.
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.fertnstert.2007.06.010. Epub 2007 Nov 5.
citation: 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.