Impact of Vaginal Microbiome on Vaginal Absorption of Exogenous Progesterone: a Pilot Study.
Condition: Infertility, Female
MeSH terms: Infertility; Infertility, Female
Study type: Interventional

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.
    

Intervention name(s): MICROBIOME GENETIC ANALYSIS; VAGINAL PH VALUE; SERUM PROGESTERONE LEVELS; SERUM OESTRADIOL LEVELS
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test
Intervention description(s): 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; Intravaginal Ph value meassurement.; 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-.; 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.
Intervention MeSH terms: Estradiol; Progesterone
Intervention model: Single Group Assignment
Intervention model description: Prospective cohort unicentric pilot study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: LUTHEAL PHASE SUPPORT; MICROBIOME; INFERTILITY; ONGOING PREGNANCY RATE; LIFE BIRTH RATE; ARTIFICIAL REPRODUCTION TREATMENT; EMBRYO TRANSFER