Levels of L-carnitine in human seminal plasma are associated with sperm fatty acid composition.

The fatty acid composition of spermatozoa has been shown to be important for their function, and L-carnitine is crucial for fatty acid metabolism. Its levels in the seminal plasma positively correlate with semen quality, whereas high body mass index (BMI) is associated with both reduced semen quality and altered sperm fatty acid composition. Here, we examined the associations between free seminal L-carnitine levels and sperm fatty acid composition as well as BMI. Semen samples were collected and analyzed from 128 men with unknown fertility status and with BMI ranging from 19 kg m-2 to 63 kg m-2. Sperm fatty acid composition was assessed by gas chromatography, while free seminal L-carnitine analysis was performed using high-performance liquid chromatography. Multiple linear regression analysis showed a positive correlation of free seminal L-carnitine levels with the amount of sperm palmitic acid (ß = 0.21; P = 0.014), docosahexaenoic acid (DHA; ß = 0.23; P = 0.007), and total n-3 polyunsaturated fatty acids (ß = 0.23; P = 0.008) and a negative correlation of free seminal L-carnitine levels with lignoceric acid (ß = -0.29; P = 0.001) and total n-6 polyunsaturated fatty acids (ß = -0.24; P = 0.012) when adjusted for covariates. There was no relationship between free seminal L-carnitine levels and BMI. Since free seminal L-carnitine levels are associated with semen quality, the absence of a correlation with BMI suggests that reduced semen quality in obese men is independent of seminal L-carnitine.

Fragmentation of human cleavage-stage embryos is related to the progression through meiotic and mitotic cell cycles.

OBJECTIVE: To study whether fragmentation of human embryos is related to the progression through meiotic and mitotic cell cycles. DESIGN: This report consists of two observational studies. SETTING: Not applicable. PATIENT(S): A total of 1,943 oocytes from 297 patients and 372 embryos from 100 patients were imaged in the Polscope instrument and monitored in the Embryoscope, respectively. INTERVENTION(S): Completion of the first meiotic division was determined by visualization of the meiotic metaphase II spindle in human oocytes, and the duration of the first three mitotic cell cycles was determined with time-lapse microscopy. The percentage of embryo fragmentation was recorded 42-45 hours after insemination. MAIN OUTCOME MEASURE(S): Appearance of the meiotic spindle; durations of the first, second, and third mitoses. RESULT(S): Human embryos with a low degree of fragmentation (<10%) at 42-45 hours after insemination originated from oocytes with an early appearance of the meiotic spindle (mean 35.5 hours after hCG injection), early first mitosis (28.2 hours after insemination), late start of the second mitosis (38.0 hours after insemination), and a shorter duration of the third mitosis (1.1 hours). Highly fragmented embryos (>50% fragmentation) originated from oocytes with a late-appearing meiotic spindle (36.5 hours after hCG injection), delayed initiation of the first mitosis (29.8 hours after insemination), early start of the second mitosis (36.4 hours after insemination), and a longer duration of the third mitotic cell cycle (4.1 hours). CONCLUSION(S): The observed associations suggest that the process of fragmentation of in vitro-derived embryos was related to the progress of the meiotic and the mitotic cell cycles.

Advanced glycation end products and their receptor contribute to ovarian ageing.

STUDY QUESTION: Do advanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) affect the cells of the human ovarian follicle? SUMMARY ANSWER: AGE accumulate on the surface of ovarian granulosa-lutein (GL) cells and monocytes by binding to RAGE and other receptors with possible functional effects on these cells. WHAT IS KNOWN ALREADY: AGE and RAGE are expressed in granulosa and theca cells, as well as in luteinized cells derived from the ovary. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, human follicle fluid-derived cells were isolated from aspirates of ovarian follicles of women who underwent assisted reproduction treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunofluorescence microscopy and multi-colour flow cytometry were used to determine the presence of AGE and RAGE on the surface of follicular fluid-derived cells and to characterize downstream effects of RAGE activation. MAIN RESULTS AND THE ROLE OF CHANCE: GL cells and ovarian monocytes were found to contain AGE and RAGE and to bind AGE-bovine serum albumin (BSA) in correlation with the patients' chronological age. AGE-BSA and BSA failed to induce significantly the cleavage of caspase-3, phosphorylation of nuclear factor-κB or the binding of annexin V (the latter was marginally increased). AGE-fibronectin was found to induce detachment of cultured GL cells in vitro. LIMITATIONS, REASONS FOR CAUTION: The impact of AGE and RAGE in the ovary, shown here in cells in culture, remains to be affirmed in clinical settings. WIDER IMPLICATIONS OF THE FINDINGS: The ligands of RAGE and their effects in the ovary remain uncertain but this study implies that AGEs in the form of structural long-lived extracellular matrix proteins, rather than soluble AGEs, may play a role in the decline of ovarian function during ageing. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Norwegian Resource Centre for Women's Health, Oslo University Hospital. The authors have no conflicts of interests.

Do endometriomas induce an inflammatory reaction in nearby follicles?

STUDY QUESTION: Do endometriomas induce an inflammatory reaction with increased cytokine concentrations in nearby follicles and thereby affect follicular development during controlled ovarian stimulation for in vitro fertilization (IVF)? SUMMARY ANSWER: With most endometriomas, there is no evidence of increased cytokine concentrations in the ipsilateral leading follicle. Infrequently, the concentration of inflammatory cytokines is increased in the follicular fluid (FF) and associated with diminished ovarian response. WHAT IS KNOWN ALREADY: The link between peritoneal endometriosis, inflammation and infertility is well established; however, the association between intraovarian inflammation and endometrioma is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 117 infertile women undergoing IVF in a tertiary infertility clinic at Oslo University Hospital Rikshospitalet, Norway, during the period May 2009 to September 2011. PARTICIPANTS, SETTING, METHODS: There were 47 patients with unilateral endometrioma and 17 patients with bilateral endometrioma, while the 53 control patients had unexplained or male factor infertility. Concentrations of IL-1ß, IL-6, IL-8, IL-10, IL-12 and TNF-α were measured in serum and in the fluid of the largest pre-ovulatory follicles from each ovary of each participant. MAIN RESULTS AND THE ROLE OF CHANCE: Cytokine levels in the follicular fluid from the two ovaries in women with unilateral endometriomas were comparable, and were not significantly altered compared with that of control groups with male factor infertility, unexplained infertility or bilateral endometriomas. Compared with serum levels, the follicular fluid levels of IL-8 and IL-6 were higher, suggesting a local production or recruitment. The follicular fluid IL-8 level varied considerably and showed an inverse relationship with IL-12, IL-10 and TNF-∝, suggesting a complex interaction between various immune cells. A small group of patients (n = 3) had increased levels of all follicular fluid cytokines combined with moderately to slightly elevated serum levels and these patients had a significantly lower ovarian response. LIMITATIONS, REASONS FOR CAUTION: For ethical reasons, the endometriomas were diagnosed indirectly by ultrasound rather than by histology. WIDER IMPLICATIONS OF THE FINDINGS: This paper reveals that endometriomas seldom induce inflammation in nearby follicles during IVF; therefore, routine cystectomy prior to IVF may not be necessary. Cytokine levels in the follicular fluid, nonetheless, show distinctive patterns and increased levels may be linked to reduced ovarian response independent of the cause of infertility.

Routine morphological scoring systems in assisted reproduction treatment fail to reflect age-related impairment of oocyte and embryo quality.

Routine morphological scoring systems in assisted reproduction treatment are based on parameters that presumably correlate with the biological quality of gametes and embryos, including chromosome abnormalities. Maternal age is a key factor predicting pregnancy and live birth, and it is therefore of considerable interest to identify age-related indicators of oocyte and embryo quality in assisted reproduction treatment. The purpose of this study was to examine whether routine morphological scoring systems reflect age-related impact on oocyte and embryo quality among 4587 couples undergoing their first assisted reproduction treatment. This study assessed over 43,000 oocytes, 25,000 embryos and 7900 transferred embryos and analysed the associations among the following parameters: number of oocytes retrieved, oocyte quality, including maturity, fertilization rates, embryo quality, based on morphological features, and treatment outcome. Advanced chronological age was found to be associated with fewer oocytes retrieved, fewer embryos available for cryopreservation, as well as lower pregnancy, implantation, live birth rates and a higher miscarriage rate. No age-related correlation was found between fertilization rates, oocyte or embryo quality. Routinely-used morphological scoring systems, such as assessment of blastomere count, shape and fragmentation, fail to reflect age-related impact on oocyte and embryo quality.