Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer

NCT ID: NCT06307184

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 530 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-23
• Study Completion Date: 2026-12-31

Brief 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.

Detailed 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.

Conditions

Frozen Embryo Transfer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Natural proliferative phase frozen embryo transfer (NPP-FET)

When the endometrial thickness is at least 7 mm, vaginal micronized progesterone will be initiated at 400mg every 12 hours, as per standard clinical practice, 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. One embryo will be transferred on the fifth day of progesterone supplementation under ultrasound guidance. Progesterone will be continued until the 11th week of pregnancy.

Natural proliferative phase frozen embryo transfer

Intervention Type: PROCEDURE

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.

Natural cycle frozen embryo transfer (NC-FET)

When the mean dominant follicle diameter was at least 17 mm and the endometrial thickness was at least 7 mm, serum E2, progesterone and luteinizing hormone (LH) were evaluated. If a spontaneously LH peak was detected (E2\>80 pg/ml, LH peak \>18 mIU/mL with progesterone level \<1.5 ng/mL), vaginal micronized progesterone was started from the evening of ovulation at a dose of 200 mg every 12 hours. Conversely, whenever a LH peak was not detected (E2\>80 pg/ml, LH \<18mIU/ml and progesterone \<1,5 ng/ml), r-hCG 250µg (Ovitrelle®) was administered subcutaneously, followed, 48 hours later, by daily administration of 200 mg micronized vaginal progesterone every 12 hours. One embryo was transferred 7 days after r-hCG administration or 6 days after LH peak detection. Progesterone was continued until the 8th week of pregnancy.

No interventions assigned to this group

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gedeon Richter Ltd.

INDUSTRY

Sponsor Role: collaborator

Instituto Valenciano de Infertilidade de Lisboa

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ana R Neves, MP

Role: PRINCIPAL_INVESTIGATOR

Instutito Valenciano de Infertilidade de Lisboa (IVI-RMA Lisboa)

Locations

Instituto Valenciano de Infertilidade

Lisbon, , Portugal

Site Status: RECRUITING

Countries

Portugal

Central Contacts

Ana R Neves, MD, PhD

Role: CONTACT

ana.neves@ivirma.com

218 503 210 ext. 00351

Facility Contacts

Samuel Santos-Ribeiro, MD PhD

Role: primary

Other Identifiers

2301-LIS-007-AN

Identifier Type: -

Identifier Source: org_study_id