Impact of semen microbiota on the composition of seminal plasma.

Several studies have found associations between specific bacterial genera and semen parameters. Bacteria are known to influence the composition of their niche and, consequently, could affect the composition of the seminal plasma. This study integrated microbiota profiling and metabolomics to explore the influence of seminal bacteria on semen metabolite composition in infertile couples, revealing associations between specific bacterial genera and metabolite profiles. Amino acids and acylcarnitines were the predominant metabolite groups identified in seminal plasma. Different microbiota profiles did not result in globally diverse metabolite compositions in seminal plasma. Nevertheless, levels of specific metabolites increased in the presence of a dysbiotic microbiota. Urocanate was significantly increased in abnormal semen samples (adjusted P-value < 0.001) and enriched in samples dominated by Prevotella spp. (P-value < 0.05), which was previously linked to a negative impact on semen. Therefore, varying microbiota profiles can influence the abundance of certain metabolites, potentially having an immunomodulatory effect, as seen with urocanate.IMPORTANCEMale infertility is often considered idiopathic since the specific cause of infertility often remains unidentified. Recently, variations in the seminal microbiota composition have been associated with normal and abnormal semen parameters and may, therefore, influence male infertility. Bacteria are known to alter the metabolite composition of their ecological niches, and thus, seminal bacteria might affect the composition of the seminal fluid, crucial in the fertilization process. Our research indicates that distinct seminal microbiota profiles are not associated with widespread changes in the metabolite composition of the seminal fluid. Instead, the presence of particular metabolites with immunomodulatory functions, such as urocanate, could shed light on the interplay between seminal microbiota and variations in semen parameters.

Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level.

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.

Male infertility: the intracellular bacterial hypothesis.

Infertility is a disease that affects one in seven couples. As male infertility affects approximately 30% of these couples with an unknown cause in half the cases, it represents a major public health concern. The classic treatment of male infertility involves intrauterine insemination, with modest outcome, and in vitro fertilization with intracytoplasmic sperm injection, which is known to be invasive and expensive, without treating the specific cause of infertility. Male fertility is mainly evaluated through a semen assessment where abnormal parameters such as concentration and motility can be associated with a decreased chance of conception. Infectious processes represent plausible candidates for male infertility. Chlamydia trachomatis is well known to cause female infertility through tubal damage but its role in male infertility remains controversial. The link between ureaplasmas/mycoplasmas and male infertility is also debatable. The potential negative impact of these bacteria on male fertility might not only involve semen parameters but also, as with C. trachomatis, include important physiological mechanisms such as fertilization processes that are not routinely assessed during infertility investigation. Basic research is important to help determine the exact effect of these bacteria on male fertility to develop targeted treatment and go beyond in vitro fertilization with intracytoplasmic sperm injection.

Waddlia chondrophila, a Chlamydia-related bacterium, has a negative impact on human spermatozoa.

STUDY QUESTION: What is the impact of Waddlia chondrophila, an emerging Chlamydia-related bacterium associated with miscarriage, on human spermatozoa? SUMMARY ANSWER: W. chondrophila had a negative impact on human spermatozoa (decrease in viability and mitochondrial membrane potential) and was not entirely removed from infected samples by density gradient centrifugation. WHAT IS KNOWN ALREADY: Bacterial infection or colonization might have a deleterious effect on male fertility. Waddlia chondrophila was previously associated with miscarriage, but its impact on male reproductive function has never been studied. STUDY DESIGN SIZE, DURATION: An in vitro model of human spermatozoa infection was used to assess the effects of W. chondrophila infection. Controls included Chlamydia trachomatis serovar D and latex beads with similar size to bacteria. PARTICIPANTS/MATERIALS, SETTING, METHODS: Purified motile spermatozoa were infected with W. chondrophila (multiplicity of infection of 1). Immunohistochemistry combined with confocal microscopy was used to evaluate how bacteria interact with spermatozoa. The impact on physiology was assessed by monitoring cell viability, mitochondrial membrane potential and DNA fragmentation. MAIN RESULTS AND THE ROLE OF CHANCE: Using super-resolution confocal microscopy, bacteria were localized on spermatozoa surface, as well as inside the cytoplasm. Compared to controls, W. chondrophila caused a 20% increase in mortality over 72 h of incubation (P < 0.05). Moreover, higher bacterial loads significantly reduced mitochondrial membrane potential. Bacteria present on spermatozoa surface were able to further infect a cell-monolayer, indicating that sperm might vector bacteria during sexual intercourse. LIMITATIONS REASONS FOR CAUTION: The main limitation of the study is the use of an in vitro model of infection, which might be too simplistic compared to an actual infection. An animal model of infection should be developed to better evaluate the in vivo impact of W. chondrophila. WIDER IMPLICATIONS OF THE FINDINGS: Intracellular bacteria, including C. trachomatis, Mycoplasma spp. and Ureaplasma spp., are associated with male infertility. Waddlia chondrophila might represent yet another member of this group, highlighting the need for more rigorous microbiological analysis during investigations for male infertility. STUDY FUNDING/COMPETING INTEREST(S): This work has been funded by the Department of Obstetrics and Gynecology, Lausanne University Hospital, Switzerland, and by the Swiss National Science Foundation (Grant nos. 310030-156169/1, 320030-169853/1 and 320030-169853/2 attributed to D.B.). D.B. is also supported by the 'Fondation Leenaards' through the 'Bourse pour la relève académique', by the 'Fondation Divesa' and by the 'Loterie Romande'. No conflicts of interest to declare.

[Fertility preservation techniques in women of reproductive age ]. / Techniques de préservation de la fertilité chez la femme en âge de procréer.

As a result of advances in oncologic treatment, a growing number of women diagnosed with cancer may envisage cure. Young women diagnosed with cancer often have a desire to fall pregnant in the future or may even be diagnosed with cancer in the process of family planning. The potential gonadotoxic effect of certain chemotherapeutic agents is well described. Therefore, it is essential that all women concerned about their fertility receive counselling from a reproductive medicine specialist to discuss the fertility preservation options. Currently, ovarian stimulation with cryopreservation of oocytes or fertilized oocytes is the treatment of choice. However, other options such as in vitro maturation or ovarian tissue cryopreservation should be discussed if ovarian stimulation is contraindicated.

[Management of endometrioma, recto-vaginal and bladder endometriosis]. / Prise en charge des endométriomes et de l'endométriose recto-vaginate et vésicate.

Endometriosis is a frequent, benign, chronic disease associated with pain and/or infertility. Classically the lesions are found on the pelvic peritoneum, ovary (endometrioma), rectovaginal septum and bladder. Management of endometrioma has evolved over the last few years to individualised treatment. Indeed endometrioma cystectomy can decrease pain and the risk of recurrence but is also associated with a decrease in ovarian reserve. A multi-disciplinary team should manage recto-vaginal or bladder endometriosis. Surgical resection of these lesions must be as complete as possible and can be complex.

[Reproductive endocrinology and infertility in the light of 20 years of IVF experience]. / Endocrinologie gynécologique et infertilité à la lumière de vingt ans de FIV.

In vitro fertilization (IVF)'s results have continuously improved over the past 20 years, making IVF part of routine services offered by most medical communities. The simplification of medical (ultrasound guided oocyte aspirations) and biological techniques (ready made media) contributed to the widespread development of IVF in the private sector, including in Switzerland. This challenges the needs of maintaining academic based IVF programs in the French speaking Switzerland. We believe however that IVF should remain part of academic gynecology because it also brings widespread collateral benefits that serve Gynecology notably, for teaching. Yet, the restricted size the French speaking Switzerland calls for creative approaches.

[When should we treat infertility and how should we determine the degree of urgency?]. / Quand traiter l'infertilité et comment déterminer le degré d'urgence?

The successes of assisted reproductive treatments (ART) have been amply documented. Yet, there is no clear consensus as to who are the couples who need ART and with which degree of urgency, short of course of those suffering from definitive tubal infertility or severe male factor. Determining the degree of medical urgency for deploying ART approaches is of true clinical concern. In case of occult forms of ovarian failure (not symptomatic short of infertility itself), delaying treatment may lead to definitive failure. Conversely, if infertility results from ovulatory disorders brought by stress, postponing ART for a few months may bring spontaneous pregnancies. The recent introduction of anti-mullerian hormone (AMH) testing is of significant help for assessing the degree of ovarian reserve.

[Synchronisation of the menstrual cycle and ovarian follicles: interest and benefit]. / Synchronisation du cycle menstruel et des follicules ovariens: de nombreux avantages.

In the menstrual cycle, a slight elevation of plasma FSH levels, the inter-cycle FSH signal, initiates the 1st phase of follicular recruitment. In ovarian stimulation for IVF, exogenous FSH aims at increasing the amplitude of this signal while maintaining FSH levels elevated, in order to fool the natural mechanisms of single follicular dominance. Synchronization consists in maintaining plasma FSH levels low so that all recruitable follicles remain at a resting state, prior to inducing ovarian stimulation. Practically speaking, synchronization of ovarian follicles allows to optimize clinical efforts, reduces the risk of cyst formation and ultimately, helps improving IVF outcome.