Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer

Frozen Embryo Transfer Clinical Trial

Official title:

Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer: an Ambispective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06307184
• Other study ID #: 2301-LIS-007-AN
• Status: Recruiting
• Start date: February 23, 2024
• Est. completion date: July 2025

Study information

• Verified date: March 2024
• Source: Instituto Valenciano de Infertilidade de Lisboa
• Contact: Ana R Neves, MD
• Phone: 915227816
• Email: anaraquel.lneves[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will assess the convenience of the natural proliferative phase frozen embryo transfer (NPP-FET) in terms of number of number of appointments needed before cycle scheduling.

Description:

Frozen embryo transfer (FET) is increasingly used nowadays in Assisted Reproductive Techniques (ART) clinics. Several factors account for this uprising. Among them, the concept of ovarian hyperstimulation syndrome (OHSS)-free clinic, the increasing use of preimplantation genetic testing (PGT), the improved vitrification systems, and the growing evidence regarding similar, or even better, pregnancy rates when FET are compared to fresh embryo transfers.

In the last few years, research has focused on the selection of the best protocol for endometrial preparation in patients undergoing FET cycles. Despite the accumulating evidence suggesting similar reproductive outcomes following both artificial cycle (AC-FET) and natural cycle (NC-FET) protocols, AC-FET is frequently adopted in ART centers due to its convenience in terms of cycle scheduling. However, a role for the corpus luteum in the maternal vasodilatory changes of early pregnancy has recently been associated with a decreased risk of pre-eclampsia. In fact, several large cohort studies have reported a higher risk of hypertensive diseases of pregnancy, macrosomia, post-term delivery and cesarean section following AC-FET.

The NPP-FET protocol is a strategy that potentially allows for cycle scheduling while maintaining the benefits of the natural cycle in terms of pregnancy outcomes. The main goal of the present study is to analyze its convenience in terms of the number of appointments needed before FET scheduling by comparing it with the NC-FET protocol. Additionally, the investigators aim to compare the reproductive outcomes between the two strategies and to analyze whether NPP-FET patients undergo ovulation.

Briefly, the study group will prospectively recruit ovulatory patients who will perform vaginal ultrasound monitoring will be performed on cycle day 8-12, depending on the length of the patients' menstrual cycle. When the endometrial thickness is at least 7 mm and the dominant follicle is at least 13 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. The control group will include a retrospective cohort of ovulatory patients who underwent NC-FET.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 530
• Est. completion date: July 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• Endometrial thickness = 7 mm on the day of starting progesterone-based luteal phase support (LPS)

• Serum progesterone levels <1.5 ng/ml on the day of starting progesterone-based LPS

• LPS with micronized progesterone 400mg b.i.d.

• Regular cycles (>24 days, = 38 days)

• IVF/ICSI with donated oocytes

• Single blastocyst stage embryo transfer

• First or second embryo transfer from the same cohort

Exclusion Criteria:

• Use of exogenous ovarian stimulation during FET

• Untreated hydrosalpinx, polyp, submucous myomas or severe adenomyosis

• Recurrent pregnancy loss (= 3 previous pregnancy losses)

• Recurrent implantation failure with embryos from oocyte donation (= 3 previous failed embryo transfers)

• Personalized initiation of exogenous progesterone according to a previous endometrial receptivity assay test

Related Conditions & MeSH terms

• Frozen Embryo Transfer

Intervention

Procedure:
• Natural proliferative phase frozen embryo transfer
When endometrial thickness is above 7 mm, vaginal micronized progesterone will be administered 400mg 12/12h when the dominant follicle is at least 13 mm, serum estradiol (E2) levels are >80 pg/ml, and serum progesterone levels are <1.5ng/ml. Embryo transfer will be performed on the fifth day of progesterone.

Locations

Country	Name	City	State
Portugal	Instituto Valenciano de Infertilidade	Lisboa

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Valenciano de Infertilidade de Lisboa	Gedeon Richter Ltd.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Relaxin-2 levels	Serum Relaxin-2 levels (colateral study)	5 weeks
Other	Serum Luteinizing Hormone (LH) levels	Serum LH levels (colateral study)	5 days
Primary	Number of appointments needed before cycle scheduling	Number of visits for cycle monitoring until embryo transfer scheduling	Up to three weeks
Secondary	Cycle duration until embryo transfer (days)	Number of days since the first day of menstrual bleeding until the day of embryo transfer	Up to four weeks
Secondary	Proportion of patients with low progesterone values on the day of embryo transfer	Percentage of patients with low serum progesterone levels on the day of embryo transfer	One day
Secondary	Human corionic gonadotropin (hCG) positive rate	Proportion of patients with a positive hCG test	10-14 days after ET
Secondary	Miscarriage rate	Proportion of patients with spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age	Up to 20 weeks after ET
Secondary	Ongoing pregnancy rate	Proportion of patients with a pregnancy beyond the 11th week	9-11 weeks after ET
Secondary	Live birth rate	Proportion of patients with a live birth	40 weeks after ET