Clinical trial NCT05161338: Impact of Vaginal Microbiome on Vaginal Absorption of Exogenous Progesterone: a Pilot Study.
Official title: Impact of Vaginal Microbiome on Vaginal Absorption of Exogenous Progesterone: a Pilot Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility, Female
Keywords: LUTHEAL PHASE SUPPORT
MICROBIOME
INFERTILITY
ONGOING PREGNANCY RATE
LIFE BIRTH RATE
ARTIFICIAL REPRODUCTION TREATMENT
EMBRYO TRANSFER
Lead sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
Sponsor class: OTHER
First posted: 2021-12-17
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective cohort unicentric pilot study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 -

Primary outcomes:
measure: Vaginal Microbiome
timeFrame: 12 months
Secondary outcomes:
measure: Live birth
timeFrame: 12 months
measure: Ongoing Pregnancy Rate
timeFrame: 12 months
measure: Clinical Pregnancy
timeFrame: 12 months
measure: Serum progesterone value
timeFrame: 12 months
measure: Vaginal PH
timeFrame: 12 months
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Ivi Valencia
Study officials:
References: