The Endometrial Microbiota: Challenges and Prospects.

Contrary to popular belief, we have known for many years that the endometrium is not a sterile environment and is considered to be a low-biomass milieu compared to the vagina. Numerous trials and studies have attempted to establish a valid sampling method and assess its physiological composition, but no consensus has been reached. Many factors, such as ethnicity, age and inflammation, can influence the microbiome. Moreover, it possesses a higher alpha-diversity and, therefore, contains more diverse bacteria than the vagina. For instance, Lactobacillus has been shown to be a predominant genus in the vaginal microbiome of healthy women. Consequently, even if a majority of scientists postulate that a predominance of Lactobacillus inside the uterus improves reproductive outcomes, vaginal contamination by these bacteria during sampling cannot be ruled out. Certain pathologies, such as chronic endometritis, have been identified as inflammation perpetrators that hinder the embryo implantation process. This pro-inflammatory climate created by dysbiosis of the endometrial microbiota could induce secondary inflammatory mediators via Toll-like receptors, creating an environment conducive to the development of endometriosis and even promoting carcinogenesis. However, studies to this day have focused on small populations. In addition, there is no clearly defined healthy uterine composition yet. At most, only a few taxa have been identified as pathogenic. As sampling and analysis methods become increasingly precise, we can expect the endometrial microbiota to be incorporated into future diagnostic tools and treatments for women's health.

Implantation Failure in Endometriosis Patients: Etiopathogenesis.

Embryo implantation requires adequate dialogue between a good quality embryo and a receptive endometrium. This implantation is still considered as the black box of reproductive medicine. Endometriosis is a highly prevalent chronic inflammatory disease, concerning about 10% of women of reproductive age and is one of the major causes of female infertility. The mechanisms involved in endometriosis-related infertility, an event not yet completely understood, are multifactorial and include anatomical changes, reduction in ovarian reserve, endocrine abnormalities, genetic profile, immunity markers, inflammatory mediators, or altered endometrial receptivity. In this article, we will focus on the impact of endometriosis on embryo quality and on endometrial receptivity. Results: Poor oocyte and embryo quality seem to promote a lower pregnancy rate, more than the endometrium itself in women with endometriosis. Other studies report the contrary. In addition, hormonal imbalance observed in the endometrium could also alter the embryo implantation. Conclusions: Controversial results in the literature add difficulties to the understanding of the mechanisms that lead to embryo implantation disorders. Furthermore, either oocyte/embryo impairment, altered endometrium, or both may cause impaired implantation. New prospective, randomized, and controlled studies are necessary to determine the origin of the defects that make conception more difficult in the case of endometriosis and adenomyosis.

Oocyte Cryopreservation in Patients with Endometriosis: Current Knowledge and Number Needed to Treat.

The rise of oocytes cryopreservation (OOC) in assisted reproductive techniques allows fertility preservation (FP) in an increasing number of indications. Endometriosis, a highly prevalent disease, potentially impairing ovarian reserve, seems, therefore, an interesting indication for it. The purpose of this study is to summarize the available evidence concerning FP by OOC in women with endometriosis and to calculate the number needed to treat (NNT). In total, 272 articles related to this topic were identified in PubMed. Eight studies were eligible for the review. In order to shed some light, a SWOT analysis was performed and the argument pros and cons were developed. The NNT calculated of OOC was 16, meaning that 16 women need to perform an OOC for one of them to have a child that she would not have had without this technique. In conclusion, OOC must be discussed with patients who suffer from endometriosis since it is an effective technique of FP, which can allow these patients to succeed a pregnancy that they otherwise would not have achieved. Nevertheless, it should not be performed in all patients as there is still a lack of robust socio-economic and risk-benefit data.

Comparison between paraffin and mineral oil covering on early human embryo culture: a prospective randomized study.

The oil overlay in microdrop culture systems prevents medium evaporation, helps to maintain appropriate pH and osmotic conditions and protects from microbial contamination. In the present study, we prospectively compared covering by Ovoil™, a paraffin oil, and LiteOil®, a mineral oil, on the in vitro development of human embryos and their suitability for transfer/freezing at day 3 and live birth rate. One hundred and one patients undergoing in vitro fertilization (IVF) treatment by  intracytoplasmic sperm injection (ICSI) were enrolled in our study. After ICSI, 1237 oocytes were 1:1 randomly allocated into 2 groups according to the type of overlaying oil: Ovoil™ (616 oocytes) or LiteOil® (621 oocytes). Fertilization rate was assessed around 18 hours post-insemination (hpi) and embryos were checked for early cleavage at 25 hpi. Embryo morphology was recorded on days 2 and 3. A total of 437 (Ovoil™) and 438 day 3 embryos (LiteOil®) were analyzed. There were no differences between the two groups in terms of fertilization rate and occurrence of early cleavage. The proportion of top quality embryos (41.7% vs. 41.2%) and the final utilization rates (92.2% vs. 92.0%) were similar in Ovoil and LiteOil groups, respectively, at day 3. Live birth rate per transfer was essentially the same with Ovoil™ overlay (26.9%) when compared to LiteOil® (26.2%). Live birth rate in patients who simultaneously received  embryos from both overlay types was 17.2%. Despite the different characteristics of these two oils regarding hydrocarbon saturation, packing and temperature storage, Ovoil™ and LiteOil® can be used in parallel in the same IVF protocol. Abbreviations: ART: assisted reproductive technologies; hpi: hours post-insemination; hSA: human serum albumin; HTF: human tubal fluid; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilization; MII: metaphase II; MEA: mouse embryo assay; RT: room temperature.

Impact of high magnification sperm selection on neonatal outcomes: a retrospective study.

PURPOSE: The aim of this study was to compare the effect of the deselection of spermatozoa presenting vacuole-like structures using IMSI (intracytoplasmic morphologically selected sperm injection) with ICSI (intracytoplasmic sperm injection) by means of neonatal outcomes. METHODS: In a retrospective two-center analysis, a total of 848 successful IMSI or ICSI cycles ending with a live birth, induced abortion, or intrauterine fetal death (IUFD) were included. RESULTS: The IMSI and ICSI groups included 332 and 655 babies or fetuses, respectively. The parents were older in the IMSI group than in the ICSI group (mothers were 35.1 vs 32.9 years, and fathers were 39.1 vs 36.2 years). The multiple pregnancy rate was higher in the IMSI group. The mean pregnancy duration and mean birth weight were almost identical in both groups. There was no significant difference in major congenital malformations between the two groups. However, this rate was decreased in the IMSI group compared to that in the ICSI group (1.8 vs 3.2%), the difference being mainly found in singletons (1.4 vs 3.3%). Boys were more often affected than girls in both groups. The percentages of chromosomal abnormalities did not differ between the IMSI and ICSI groups (0.6 and 0.8%). The reported congenital malformations mainly affected the heart, urogenital, and musculoskeletal systems. CONCLUSIONS: In the present study, the malformation rates observed in the IMSI and ICSI groups were not significantly different, even if slightly lower after IMSI. However, the observed difference followed the same trends observed in previous reports, indicating the possible impact of IMSI on decreasing congenital malformation occurrences. This highlights the necessity to prospectively evaluate the impact of IMSI on neonatal outcome after IVF treatment.

Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time.

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular endometrial bleeding. Metalloproteinases contribute to extracellular matrix (ECM) remodelling and regulate bleeding during the menstrual cycle. Enhanced metalloproteinase expression participates in the pathogenesis of breakthrough bleeding. Thus the objective of this study was to compare matrix metalloproteinase (MMP) expression in endometrium during luteal phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users. METHODS: MMP expression was analysed by semi-quantitative RT-PCR and immunohistochemistry. Gelatinase activity was determined by gelatin zymography. RESULTS: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7 and -9 were localized by immunohistochemistry in all biopsies in the short-term group but in only 0-27% in the control group. The incidence of positive immunostaining for MMP-2 and -3 decreased significantly in the long-term compared with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the control group but in only 14 and 25% from the short- and long-term LNG-IUS groups, respectively. In both LNG groups, the numbers of macrophages (the major source of MMP-12) was increased. CONCLUSIONS: MMP-1, active MMP-2, MMP-3, MMP-7, MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting their important contribution to ECM breakdown and transient bleeding. The decrease in the percentage of women expressing MMP-2 and -3 might contribute to the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS users.