The impact of caesarean scar niche on fertility - a systematic review.

BACKGROUND: The trend of increasing caesarean section (CS) rates brings up questions related to subfertility. Research regarding the influence of CS on assisted reproduction techniques (ART) is conflicting. A potential mechanism behind CS-induced subfertility is intra uterine fluid resulting from a caesarean scar defect or niche. The vaginal microbiome has been repeatedly connected to negative ART outcomes, but it is unknown if the microbiome is changed in relation to a niche. METHODS: This systematic review describes literature investigating the effect of a niche on live birth rates after assisted reproduction. Furthermore, studies investigating a difference in microbial composition in subfertile persons with a niche compared to no niche are evaluated. Pubmed, Embase and Web of Science were searched on March 2023 for comparative studies on both study questions. Inclusion criteria were i.e., English language, human-only studies, availability of the full article and presence of comparative pregnancy data on a niche. The quality of the included studies and their risk of bias were assessed using the Newcastle-Ottawa scale for cohort studies. The results were graphically displayed in a forest plot. RESULTS: Six retrospective cohort studies could be included on fertility outcomes, with a total of 1083 persons with a niche and 3987 without a niche. The overall direction of effect shows a negative impact of a niche on the live birth rate (pooled aOR 0.58, 95% CI 0.48-0.69) with low-grade evidence. Three studies comparing the microbiome between persons with and without a CS could be identified. CONCLUSION: There is low-grade evidence to conclude that the presence of a niche reduces live birth rates when compared to persons without a niche. The theory that a caesarean has a negative impact on pregnancy outcomes because of dysbiosis promoted by the niche is interesting, but there is no sufficient literature about this.

The increasing number of caesarean deliveries has raised concerns about how it might affect a woman's ability to get pregnant afterwards. Some studies suggest that having a caesarean section (CS) could make it harder to conceive, particularly through in vitro fertilisation (IVF). The reason could be the scar or niche from a previous caesarean. This niche can cause fluid inside the uterus. We also know that the mix of bacteria in the vagina, called the vaginal microbiome, can affect a woman's chances of getting pregnant, especially with treatments like IVF. But we are not sure if having a caesarean affects the vaginal microbiome.To understand this better, van den Tweel's team looked at studies on whether having a niche from a caesarean affects a woman's chance of having a baby through IVF. They also looked at studies comparing the bacteria in the vagina of women who have had a caesarean with those who have not. They found that having a caesarean niche makes it harder for a woman to have a baby through IVF. However, the evidence from these studies is not very strong. We still do not know enough about whether having a caesarean niche affects the bacteria in the vagina.

The Vaginal Microbiome Changes During Various Fertility Treatments.

This study aimed to investigate the influence of hormonal treatment on the vaginal microbiome during fertility treatments. Bacterial vaginosis (BV) could affect fecundity, particularly in the in vitro fertilization (IVF) population, where negative effects on pregnancy outcomes have been reported. It is hypothesized that the hormone treatment during fertility treatments could influence the abundance of Lactobacilli, with negative effects on the pregnancy results. A total of 53 couples attending a fertility clinic in the Netherlands between July 2019 and August 2022 were included in this prospective cohort study. Vaginal samples were collected at start of treatment, oocyte retrieval or insemination from subjects undergoing intra uterine insemination (IUI) with mild ovarian stimulation, and IVF or intra cytoplasmatic sperm injection (ICSI) with controlled ovarian hyperstimulation. AmpliSens® Florocenosis/Bacterial vaginosis-FRT qPCR and 16S rRNA gene-based amplicon sequencing were performed on all samples. In total, 140 swabs were analyzed, with a median of two swabs per person. 33 (24%) tested qPCR BV positive. Lactobacilli percentage decreased during fertility treatments, leading to changes in the vaginal microbiome. Shannon diversity index was not significantly different. Of the total of 53 persons, nine switched from qPCR BV negative to positive during treatment. The persons switching to qPCR BV positive had already a (not significant) higher Shannon diversity index at start of treatment. If the vaginal microbiome of persons deteriorates during fertility treatments, timing of following treatments, lifestyle modifications, or a freeze all strategy could be of possible benefit.

The relationship between vaginal pH and bacterial vaginosis as diagnosed using qPCR in an asymptomatic subfertile population.

PURPOSE: Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome and a condition found in 20-30% of all women. Literature describing the possible link between BV and subfertility is increasing. Newer techniques such as quantitative polymerase chain reactions (qPCR) detect BV more accurately than traditional methods but come with high costs. The association between pH and BV as diagnosed using traditional methods is well-established in a symptomatic population. This study is the first to investigate the association between pH and BV diagnosed by qPCR in an asymptomatic subfertile population and to examine the usefulness of pH as a means of cost reduction. METHODS: Data of 170 pH-qPCR combinations were used from a prospective cohort study examining bacterial vaginosis in a subfertile population. 102 women received a vaginal swab and pH measurement at baseline and subsequent advanced reproductive technology (ART) treatments. The swabs are analysed using the AmpliSens®Florocenosis/Bacterial vaginosis-FRT qPCR kit. RESULTS: pH is strongly associated with BV as diagnosed by qPCR (OR 3.06, p = 0.000, CI 1.65-5.68). The cut-off point for pH ≥ 4.7 maximised diagnostic performance [AUC 0.74 (CI 0.66-0.83), sensitivity 76%] and reduced costs by 60%. CONCLUSION: This study shows that the vaginal pH for a multi-ethnic, asymptomatic population of women attending fertility clinics is strongly associated with BV qPCR outcome. Using the cut-off of pH of 4.7 has a high sensitivity for diagnosis of BV by qPCR and can be achieved at a cost reduction of 60%.