Impact Of FET Preparation Protocol On Endometrial Peristalsis: A Prospective Cohort Study (EPFE)

Mỹ Đức Hospital

Status: Not yet enrolling

Conditions: Uterine Contraction; Endometrial Peristalsis; Infertility; Uterine Peristalsis; Frozen Embryo Transfer (FET); Endometrial Waves

Treatments: Other: Endometrial peristalsis and hormone measurements

Study type: Observational

Funder types: Other

Identifiers

NCT07358468

18/25/DD-BVMD

Details and patient eligibility

About

The uterus is a dynamic muscular organ that undergoes rhythmic, wave-like contractions known as endometrial peristalsis or endometrial waves. This muscular activity, which is an essential component of natural fertility, presents a nuanced and sometimes contradictory role in the context of assisted reproductive treatments. Endometrial peristalsis refers to the frequency, amplitude, and pattern of myometrial contractions occurring in different reproductive phases. These peristalsis play vital roles in sperm transport, embryo migration, and implantation. Clinical and imaging studies suggest that abnormal patterns or excessive contractility at the time of embryo transfer may disrupt endometrial-embryo synchrony, impair implantation, and increase miscarriage risk. However, most evidence on endometrial peristalsis pertains to fresh embryo transfer cycles, natural conceptions, or pathological contexts, such as adenomyosis or fibroids, with limited insights regarding its effects on different endometrial preparation protocols in frozen embryo transfer (FET). Understanding the dynamics of endometrial peristalsis in this context is clinically important, as inappropriate contractile activity could physically expel the embryo or create a non-receptive environment, ultimately reducing the chances of live birth. Despite its theoretical significance, there is a paucity of robust, prospective data correlating endometrial peristalsis patterns measured around the time of FET with different endometrial preparation protocols with subsequent pregnancy outcomes.

Full description

The uterus is a dynamic muscular organ that undergoes rhythmic, wave-like contractions known as endometrial peristalsis or endometrial waves. This muscular activity, which is an essential component of natural fertility, presents a nuanced and sometimes contradictory role in the context of assisted reproductive treatments. Endometrial peristalsis refers to the frequency, amplitude, and pattern of myometrial contractions occurring in different reproductive phases. These peristalsis play vital roles in sperm transport, embryo migration, and implantation.

Clinical and imaging studies suggest that abnormal patterns or excessive contractility at the time of embryo transfer may disrupt endometrial-embryo synchrony, impair implantation, and increase miscarriage risk. However, most evidence on uterine contractility pertains to fresh embryo transfer cycles, natural conceptions, or pathological contexts, such as adenomyosis or fibroids, with limited insights regarding its effects on different FET protocols. Several studies have demonstrated an inverse relationship between endometrial peristalsis and IVF success. Masroor et al. found that patients with lower endometrial peristaltic wave frequency (<4 waves/min) before embryo transfer had significantly higher chances of clinical pregnancy and live birth compared to those with more frequent peristalsis. Similarly, Chung et al. reported that increased endometrial peristalsis frequency immediately after embryo transfer was linked to reduced live birth rates, suggesting that excessive motility may physically expel the embryo or disturb its implantation. In the prospective cohort study of 292 infertile women, Zhu et al. found that lower uterine peristaltic wave frequency (<3.0 waves/min) before embryo transfer is associated with higher clinical pregnancy rates in both fresh and frozen-thawed embryo transfer cycles. In a study by Vuong et al. on patients with repeated implantation failure, they found that administering atosiban to patients with uterine peristalsis exceeding 16 waves per 4 minutes could improve pregnancy rates.

Different protocols for endometrial preparation in FET cycles, including natural cycles and hormone replacement therapy (HRT) cycles, create distinct hormonal environments that influence endometrial peristalsis and may impact pregnancy outcomes. Understanding how endometrial peristalsis varies by protocol and its effect on pregnancy outcomes is essential for optimizing IVF strategies.

Therefore, this study aims to evaluate endometrial peristalsis patterns in different FET protocols and their association with pregnancy outcomes.

Enrollment: 356 estimated patients

Sex: Female

Ages: 18 to 42 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Women aged 18 - 42 years old
• Scheduled for frozen embryo transfer cycles using hormone replacement therapy protocol or natural cycle protocol (True natural cycles or modified natural cycles)
• Transferred no more than two cleavage embryos or one good-quality blastocyst or no more than two poor-quality blastocysts

Exclusion criteria

• Having an allergy and contraindications for exogenous hormone administration (e.g., breast cancer, thromboembolic disease)
• Cycles with preimplantation genetic testing, oocyte donation, or in vitro maturation
• Having untreated uterine or adnexal abnormalities (e.g., intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus, endometrial polyp, large leiomyoma ≥5 cm in diameter, hydrosalpinx, endometrial hyperplasia).
• Use of uterine relaxants or intralipid infusion during the embryo transfer process.
• Use of a GnRH-agonist for downregulation within one month.
• PCOS patients

Trial design

356 participants in 2 patient groups

Exogenous steroid protocol

Description:

The endometrium was prepared with the use of oral estradiol valerate (Progynova®; Delpharm Lille SAS, France, or Valiera®, Laboratorios Recalcine) at a dose of 6 mg per day, starting on the second, third, or fourth day of the menstrual cycle. Endometrial thickness was monitored from day 10 onward, and vaginal progesterone (Cyclogest, LD Collins, UK) at a dose of 800 mg per day and dydrogesterone (Duphaston, Abbott Biologicals B.V, US) at a dose of 20 mg per day were started when the endometrial thickness reached 8 mm or more. Embryo transfer was performed at 4 days for cleavage embryos transfer or 6 days for blastocyst embryo transfer after starting progesterone. All embryos were warmed on the day of transfer. Vaginal progesterone administration will be maintained until the day of the pregnancy test. In the event of a positive test result, luteal phase support will be extended until 10 weeks of gestation.

Treatment:

Other: Endometrial peristalsis and hormone measurements

Natural protocol (True natural cycle or modified natural cycle)

Description:

Daily ultrasound and serum estradiol and LH level evaluation will be performed when the mean diameter of the dominant follicle of ≥14 mm. On natural cycle, LH surge initiation is defined as a concentration of 180% above the latest serum value available in that patient with a continued rise thereafter to a level of 20 IU/l or more detected by the ECLIA method (Roche Cobas® E 801, Roche Diagnostics, Germany). On modified natural cycle, when the mean diameter of the dominant follicle is ≥16 mm, human chorionic gonadotropin (hCG, Ovitrelle® 250 µg; Merck, USA) will be injected to trigger ovulation. Vaginal progesterone (Cyclogest, LD Collins, UK) at a dose of 800 mg per day was started 2 days after the LH surge/ hCG injection. Embryo transfer will be scheduled by the time of the initiation of LH and embryo stages. Vaginal progesterone administration will be maintained until the day of the pregnancy test. In the event of a positive test result, luteal phase

Treatment:

Other: Endometrial peristalsis and hormone measurements