Impact of Vaginal Microbiome on Vaginal Absorption of Exogenous Progesterone: a Pilot Study. (PROGEBIOMA)

Is already demonstrated that around 30% of patients undergoing an artificial cycle with vaginal progesterone do not reach a minimum threshold value of serum progesterone levels on the day of embryo transfer. Women with serum progesterone levels below this threshold have 20% lower ongoing pregnancy and live birth rates, decreasing their chances of success. However, the cause of this high heterogeneity in exogenous vaginal progesterone absorption among our patients remains unknown. It has been suggested that vaginal microbiome, and vaginal pH (due to its impact in microbiota growth), may explain the differences in vaginal progesterone absorption. The aim of the present pilot study is to assess if certain vaginal conditions, such as its microbiome status or its pH level, might affect vaginal progesterone absorption (measured by serum progesterone levels) and, in turn, the chances of success. In order to evaluate it, a prospective cohort unicentric study will be conducted in IVI RMA Valencia (Spain). Infertile patients undergoing an embryo transfer in the context of an artificial cycle when using vaginal progesterone will be recruited. Serum progesterone and estradiol levels, microbiome genetic analysis in vaginal samples and vaginal pH will be measured both on the embryo transfer-scheduling day and on the embryo transfer day.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Diagnostic test: MICROBIOME GENETIC ANALYSIS; Diagnostic test: VAGINAL PH VALUE; Diagnostic test: SERUM PROGESTERONE LEVELS; Diagnostic test: SERUM OESTRADIOL LEVELS

Detailed Description

Currently, as part of routine clinical practice serum progesterone levels were meassured of women undergoing an ET in the context of an artificial cycle. These blood tests are usually performed around 2 hours before ET, thus results are available before their departure of the clinic. In the event of detecting low serum progesterone levels, an extra dose of exogenous subcutaneous progesterone is given for LPS.

There is not knowing about the reason of this heterogeneity in progesterone absorption, and one plausible hypothesis is vaginal microbiome. In the event of proving a significant association between vaginal microbiome and serum progesterone levels on the day of ET, and in particular if these levels are below or above the delimited threshold, it would be possible to individualize LPS in several patients in a more direct manner.

It is true that our current clinical practice, giving subcutaneous progesterone, is capable of equaling OPR of women with serum progesterone levels below 8.8 ng/ml on the ET day to those with values above this threshold applying the exact same approach to all patients. This study could be the next step towards an iLPS, to know the reason of the lower progesterone levels, and treat it directly, instead of moving to the need of a daily injection of progesterone which is costly and not patient friendly. Furthermore, vaginal microbiome may also have an impact in the subsequent OPR, even though serum progesterone levels were over 8.8 ng/ml. If this is the case, the analisys in advance the patient's vaginal microbiome will allow to treat the patient accordingly in order to increase the results of the ART treatment.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46015
    • IVI Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The subject must provide written informed consent prior to any study related procedures
• Women ≤50 years old
• BMI ≤ 25 kg/m2
• Adequate endometrial thickness (>6.5mm) and pattern (Triple A structure) in the proliferative phase

Exclusion Criteria:

• Uterine Pathology, adnexal pathology
• Systemic diseases -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FROZEN EMBRYO TRANSFER; Women who undergo an artificial cycle for frozen embryo transfer and receive luteal phase support.

Diagnostic test: MICROBIOME GENETIC ANALYSIS; Vaginal samples will be taken. A floxed nylon swab will be rotated against the posterior vaginal wall, Nucleic acid extraction and genetic analisys will be performed; Diagnostic test: VAGINAL PH VALUE; Intravaginal Ph value meassurement.; Diagnostic test: SERUM PROGESTERONE LEVELS; Determination of serum P4 levels On the day of embryo transfer scheduling (prior to the onset of exogenous progesterone administration) and on the embryo transfer day-.; Diagnostic test: SERUM OESTRADIOL LEVELS; Determination of serum E2 levels On the day of embryo transfer scheduling (prior to the onset of exogenous progesterone administration) and on the embryo transfer day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaginal Microbiome	Result of the microbiome genetic analysis in vaginal samples (nucleic acid extraction and genetic analysis)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	Live birth rate	12 months
Ongoing Pregnancy Rate	Success value in pregnancy after ultrasound confirmation of heartbeat and 12 weeks of pregnancy	12 months
Clinical Pregnancy	Pregnancy confirmation by the observation of the presence of at least one gestational sac on ultrasound	12 months
Serum progesterone value	Serum progesterone levels	12 months
Vaginal PH	Measure of vaginal pH levels	12 months

Collaborators and Investigators

• Sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): March 1, 2023
• Study Completion (Actual): April 30, 2023

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: LUTHEAL PHASE SUPPORT; MICROBIOME; INFERTILITY; ONGOING PREGNANCY RATE; LIFE BIRTH RATE; ARTIFICIAL REPRODUCTION TREATMENT; EMBRYO TRANSFER
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Progestins; Estradiol; Progesterone
• Other Study ID Numbers: 2110-VLC-095-EL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No