Dear colleagues,

We are pleased to inform you about two interesting topics at the end of a difficult pandemic year:

• Special endometrial diagnostics in habitual abortions or recurrent implantation failure
• Influence of the genital microbiome on the success of fertility treatment

Special endometrial diagnostics for habitual abortions or recurrent implantation failure

1) At the beginning of the diagnostics, an HSK/stich curettage is performed, which is usually already arranged by you. Even if polyps or fibroids do not necessarily have to be removed if you wish to have a child, they can be a cause for the lack of pregnancy. In addition, intrauterine septa or adhesions, which occur for example after infections or previous operations, can also be a problem. In such cases, a diagnostic/therapeutic hysteroscopy is then useful. For this purpose, we cooperate with various specialized departments of regional clinics.

2) A specialized diagnostic option is testing in the endometrium for uterine natural killer cells, plasma cells (signs of chronic endometritis), and regulatory T cells (decreases in uterine regulatory T cells potentially negatively impact endometrial receptivity and implantation of the embryo). For this determination, a tissue sample of only millimeter size of the endometrium is taken by means of a pipelle on the 20th ZT or approximately 7 days after ovulation and examined in a specialized laboratory (e.g. Reprognostics in Mannheim, Uni Jena). Therapeutically, we can use prednisolone and/or Intralipid in case of elevated killer cells, perform high-dose antibiotic therapy with doxycycline in case of elevated plasma cells, or arrange for hCG flushing in case of decreased regulatory T cells before embryo transfer.

3) Another diagnostic option is the ERA test (endometrial receptivity array), in which the expression level of genes in an Endometrial sample is determined. In this test, the implantation window for the correct timing of embryo transfer after artificial fertilization. In individual cases, this can be shifted forward or backward by a few days. For this purpose, a small tissue sample is taken For this purpose, a small tissue sample is taken by means of a pipelle during the presumed period of implantation and sent to a specialized laboratory in Spain for evaluation. If necessary, the timing of the embryo transfer must be adjusted.

4) Based on the ERA test, there is the ERP test (Endometrial Receptivity Profile), which uses immunohistochemical studies to determine the implantation window for the correct time of embryo transfer. A small tissue sample of the endometrium is also taken by means of pipelle of the endometrium at the presumed time of the implantation window and evaluated in a specialized laboratory (Kaufbeuren/Ravensburg). Based on the results obtained, the time of embryo transfer can be adjusted.

Influence of the genital microbiome on the success of infertility treatment

According to recent findings, the composition of the genital microbiome also appears to play an important role in the success of fertility treatments. Infection screening of the vaginal lower genital tract can be performed and antibiotic therapy considered if necessary. Bacterial colonization of the upper genital tract, i.e., the endometrium, has not been addressed. In recent studies, there is evidence that an endometrial microbiome dominated by certain lactobacilli is a prerequisite for successful IVF or ICSI treatment. The endometrial microbiome is thought to be cycle-independent and distinct from the vaginal microbiome. Thus, especially in cases of repeated implantation failure, a precise analysis of the endometrial microbiome using „next generation sequencing“ may be useful. This allows bacteria to be determined - after comparison with corresponding databases - and the colonization of the endometrium to be specified.

It is possible that the function of lactobacilli is to influence immunoregulatory processes in the uterus by producing lactate. During implantation of the embryo, which is a semiallogenic transplantation of the embryo, such local factors seem to play a role above all. If dysbiosis is shown to be a possible cause of the fertility disorder, therapy with antibiotics and probiotics can be undertaken. Bioactive molecules, such as lactoferrin, can be supportive in this regard, so that a combined treatment enables the establishment of a lactobacillus-dominated uterine microbiome. In summary, there is growing evidence of a link between endometrial microbiome and reproductive health.

However, all these new investigations and therapeutic approaches are not yet part of the golden standard of fertility treatment and need to be further scientifically substantiated.

We thank you for your interest and the trust you have placed in us over the past year and wish you and your team a Merry Christmas and a blessed New Year 2022.

Yours sincerely, with best regards from our colleagues

Dres. med. Katharina Mayer-Eichberger, Rafaela Rangel, Kristin Simon and Dr. med. Dieter Mayer-Eichberger
as well as the entire team of the Kinderwunsch-Zentrums Stuttgart, Praxis Villa Haag