Comparison of Two Vaginal Progesterone Forms in Frozen Embryo Transfer

Official title

Comparison of Patient Satisfaction, Convenience and Tolerability Between Two Vaginal Progesterone Formulations During Frozen Embryo Transfer

Overview

The goal of this observational study is to compare two commonly used vaginal progesterone formulations - soft capsules versus pessaries - in women undergoing frozen embryo transfer (FET). The main question it aims to answer is: \- Do soft vaginal progesterone capsules provide similar or better patient satisfaction, convenience, and tolerability compared with vaginal progesterone pessaries during preparation for frozen embryo transfer? Participants undergoing FET who are prescribed vaginal progesterone as part of their endometrial preparation and luteal phase support will use one of the two formulations and complete patient-reported assessments regarding satisfaction, convenience, and tolerability. The study will also measure serum progesterone levels on the day of embryo transfer and evaluate pregnancy outcomes, including clinical pregnancy and live birth rates.

Detailed description

Over the past few decades, assisted reproductive technology (ART) treatments have seen their protocols updated by advances in cryopreservation methods, leading to the mainstream use of the frozen embryo transfer (FET) strategy (Nagy, Shapiro, \& Chang, 2020). FET protocols are generally subdivided in either natural cycle (NC-FET) or artificial cycle (AC-FET), with several centers preferring the latter due to its flexibility in scheduling and ease of monitoring. Nonetheless, previous reports positing that AC-FET may be associated with an increased risk of miscarriage and hypertensive disorders during pregnancy have put this preference into question (Roelens, et al., 2022). Having said that, the natural proliferative phase frozen embryo transfer protocol (NPP-FET) has recently be proposed as a strategy which potentially allows for easier cycle scheduling while potentially maintaining the benefits of the natural cycle in terms of safer pregnancy outcomes (Godinho, Soares, \& Ribeiro, 2021). Both AC-FET and NPP-FET protocols rely immensely on the use exogenous progesterone for luteal phase support (LPS), with the vaginal route being the most common in Europe due to its ease of use compared to intramuscular or subcutaneous alternatives.

Progesterone is a natural hormone produced mainly by the theca cells of the corpus luteum. When supplemented vaginally, endometrial progesterone concentrations reach a steady-state within 5 hours after administration, while serum progesterone levels remain elevated for about 48 hours with prolonged bioavailability (Bulletti, et al., 1997). In a systematic review of 18 randomized clinical trials comparing vaginal preparations for LPS, all tested preparations seemed to be equally effective and safe for assisted reproductive technology cycles (Child, Leonard, Evans, \& Lass, 2018). However, studies assessing patient satisfaction are lacking (Beltsos, et al., 2014). Hence, the main objective of this study is to assess the level of satisfaction as well as understand the convenience and tolerability of two of the most common vaginal LPS formulations (soft capsules versus pessaries). The study will compare satisfaction levels, convenience and tolerability, serum progesterone levels on the FET day and pregnancy rates between the two therapeutic formulations.

Interventions

• Other Vaginal progesterone soft capsules
  Whenever the endometrium is above 7 mm and serum progesterone is determined and if \<1.5ng/ml, vaginal micronized progesterone soft capsules is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (two 200 mg soft capsules). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient.
• Other Vaginal progesterone pessaries
  Whenever the endometrium is above 7 mm and serum progesterone is determined and if \<1.5ng/ml, vaginal progesterone pessaries is initiated as part of routine clinical practice for luteal phase support during AC-FET or NPP-FET cycles. Typical dose: 400 mg every 12 hours (one 400 mg pessary). The choice of progesterone for luteal phase suport will be performed according to routine clinical practice at the discretion of both the physician and patient.

Primary outcome measures

• Compare the patients' satisfaction, convenience and tolerability of two common vaginal progesterone formulations: soft capsules versus pessaries [Time frame: 5 days after starting progesterone supplementation]

Secondary outcome measures (3)

• Serum Progesterone(P4) level [Time frame: 5 days after starting progesterone supplementation]
• Clinical pregnancy rates [Time frame: 7 - 8 weeks of gestational age]
• Livebirth rates [Time frame: Livebirth after 22 completed weeks of gestational age]

Eligibility criteria

Inclusion criteria

• Age: ≥18 and <49 years old;
• Body Mass Index (BMI) ≥18.5 Kg/m2 and <30 Kg/m2;
• Planned for single blastocyst stage transfer;
• Has been prescribed two vaginal 200mg soft capsules or one 400mg pessary of progesterone, each 12hours before and after FET;
• Either AC-FET or NPP-FET.

Exclusion criteria

• Women who have previously enrolled in this study;
• Those unable to comprehend the investigational nature of the proposed study;
• Rank of FET>3;
• Use of oral/injectable corticoids.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Portugal · 1 center

• Instituto Valenciano de Infertilidade (IVI Lisboa) — Lisbon

Identifiers

NCT: NCT07461909 · 2306-LIS-122-SS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗