Clinical trial NCT06307184: Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer
Official title: Assessing the Convenience of Natural Proliferative Phase Frozen Embryo Transfer: an Ambispective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Frozen Embryo Transfer
Keywords: Endometrial preparation
Natural cycle
Progesterone
Pregnancy
Lead sponsor: Instituto Valenciano de Infertilidade de Lisboa
Sponsor class: NETWORK
Collaborators: name: Gedeon Richter Ltd.
First posted: 2024-03-12
Enrollment: 530
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: The study group will include a prospectively recruited cohort of ovulatory patients undergoing their first or second FET attempt following oocyte donation in a natural proliferative phase protocol. The control group will include a retrospective cohort of ovulatory patients undergoing a natural cycle frozen embryo transfer following oocyte donation.

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.

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

Primary outcomes:
measure: Number of appointments needed before cycle scheduling
timeFrame: Up to three weeks
Secondary outcomes:
measure: Cycle duration until embryo transfer (days)
timeFrame: Up to four weeks
measure: Proportion of patients with low progesterone values on the day of embryo transfer
timeFrame: One day
measure: Human corionic gonadotropin (hCG) positive rate
timeFrame: 10-14 days after ET
measure: Miscarriage rate
timeFrame: Up to 20 weeks after ET
measure: Ongoing pregnancy rate
timeFrame: 9-11 weeks after ET
measure: Live birth rate
timeFrame: 40 weeks after ET
Other outcomes:
measure: Serum Relaxin-2 levels
timeFrame: 5 weeks
measure: Serum Luteinizing Hormone (LH) levels
timeFrame: 5 days
Locations:
city: Lisboa
country: Portugal
facility: Instituto Valenciano de Infertilidade
Study officials:
affiliation: Instutito Valenciano de Infertilidade de Lisboa (IVI-RMA Lisboa)
name: Ana R Neves, MP
role: PRINCIPAL_INVESTIGATOR
References: