Identification of miR-30c-5p microRNA in Serum as a Candidate Biomarker to Diagnose Endometriosis.

The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.

A Randomized Controlled Intervention Trial with Danazol to Improve Telomeric and Fertility Parameters in Women with Diminished Ovarian Reserve: A Pilot Study.

Background: Most women who are treated at in vitro fertilization (IVF) clinics have trouble conceiving due to ovarian failure (OF), which seems to be associated to short telomeres and reduced or absent telomerase activity in their granulosa cells. Indeed, telomere pathways are involved in organ dysfunction. However, sexual steroids can stimulate the expression of the telomerase gene and have been successfully used to prevent telomere attrition. Thus, a strategy to improve IVF outcomes in women with OF could be telomerase reactivation using sexual steroids. Methods: We conducted a double-blind, placebo-controlled study. Patients with diminished ovarian reserve were randomized to Danazol or placebo for 3 months. We included patients with normal ovarian reserve in the study as untreated controls. Patients and controls underwent several ovarian stimulations (OSs). Telomere and IVF parameters were assessed. Results: We found that the mean telomere length in blood and the percentage of short and long telomeres were similar throughout the 3 months of treatment with Danazol. Remarkably, while the number of cells with one telomeric repeat-containing RNA (TERRA) focus decreased (p = 0.04) after the first month of Danazol treatment, the number of cells with 2 to 4 TERRA foci increased (p = 0.02). Regarding fertility, no differences were found in the antral follicle count. Interestingly, in OS performed after the trial, all Danazol-treated patients had a better MII oocyte rate compared to OS performed before the pilot study.EudraCT number: 2018-004400-19. Conclusions: Danazol treatment seemed to affect telomere maintenance, since both the number of TERRA foci and the ratio of MII oocytes changed. However, further research is needed to confirm these results.

Self-Detection of the LH Surge in Urine After GnRH Agonist Trigger in IVF-How to Minimize Failure to Retrieve Oocytes.

Research question: Urine LH testing may be useful to confirm an LH surge after the GnRH agonist (GnRHa) trigger prior to oocyte retrieval in IVF. Design: A prospective cohort study, including oocyte donors undergoing ovarian stimulation, treated with a GnRHa trigger for final oocyte maturation. Urine LH testing was performed at home, 12 h after the GnRHa trigger. In the case of a negative result, serum LH and progesterone measurements were done that same day. Donors with no serum LH peak after trigger were re-scheduled using a dual trigger, with GnRHa and hCG. Results: Three hundred and fifty nine oocyte donors were included in the analysis. Three hundred and fifty six donors had positive urine LH tests, followed by oocyte retrieval. In one case, the LH test was positive, however, no oocytes were retrieved (false positive 1/356). Three LH tests were negative in urine: in one of these three cases, LH was tested again in blood, confirming an LH rise, consistent with an optimal response to the GnRHa trigger; in the other two cases, serum LH was <15 mUI/mL, after which the oocyte retrieval was re-scheduled for 36 h after an being re-triggered, resulting in the retrieval of 19 and 22 MII oocytes, respectively. Considering the cost analysis, it would be a significantly cost-saving strategy, as blood testing would have costed 14,840€ vs. only 185.5€ in urine LH kits. Conclusions: Urinary testing of the LH surge after GnRHa trigger is easy, safe, reliable, and convenient. In addition, LH urine testing allows identifying donors and patients who could benefit from a rescue hCG trigger after an unsuccessful GnRHa trigger.

Letrozole administration during the luteal phase after ovarian stimulation impacts corpus luteum function: a randomized, placebo-controlled trial.

OBJECTIVE: To investigate the effect of letrozole-an oral aromatase inhibitor-on E(2), P, and LH levels when administered during the luteal phase after oocyte retrieval in IVF/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Prospective, randomized, placebo controlled trial. SETTING: University-affiliated private reproductive medicine center. PATIENT(S): Thirty oocyte donors undergoing standardized controlled ovarian hyperstimulation (COH) protocols. INTERVENTION(S): Patients were randomized after successful egg retrieval to receive either 2.5 mg of letrozole (Femara; Novartis, Barcelona, Spain) or a placebo (folic acid tablets). All donors were under intrauterine device (IUD) contraception. MAIN OUTCOME MEASURE(S): Serum E(2), P, and LH the day of hCG administration and days +4, +7 and +10 after ovum pick-up. RESULT(S): Donors had a comparable serum E(2) level on the day of hCG administration (1,858 vs. 2,143 pg/mL). Interestingly, levels dramatically dropped 4 days after egg retrieval, reaching a statistically significant lower level in those receiving letrozole (279 vs. 1,586 pg/mL). Again, at the next time points serum E(2) levels were significantly lower (day +7: 240 vs. 855 pg/mL and day +10: 40 vs. 448 pg/mL). No significant differences were observed in P levels, but LH serum concentrations were lower in the control group on day +7 (0.18 vs. 0.02 mIU/mL and day +10 (0.40 vs. 0.16 mIU/mL), when serum E(2) levels were higher. CONCLUSION(S): The administration of 2.5 mg of letrozole during the luteal phase has an impact on corpus luteum (CL) function. It reduces serum E(2) levels, which allows a faster recovery of LH concentration. This may be of interest not only for egg donors, but also in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who freeze all their embryos or who cancel hCG administration to reduce the potential risk that high E(2) levels pose.