Age at menarche and clinical outcomes following medically assisted reproduction (MAR): a cohort study.

Medically assisted reproduction (MAR) technologies have advanced rapidly, but in contrast to the specificity of modern approaches, they provide limited effectiveness in the management of the infertile couple. The purpose of this study was to assess the possible relationship between age at menarche and MAR outcomes of clinical pregnancy, live birth and the adverse incident of miscarriage, and to determine the offspring sex ratio according to age at menarche. In a cohort of 254 infertile couples who underwent 426 IVF/ICSI cycles, statistical analysis was performed by applying Student's t-test, chi-square test, and logistic regression models, adequately in the respective parameters and outcomes. The results indicated a strong association of age at menarche with the outcomes of clinical pregnancy (p = .0007) and live birth (p < .0001), especially by applying a threshold of 12 years in the first occurrence of menstruation (p = .0019 for clinical pregnancy, p < .0001 for live birth), also demonstrating a negative effect for earlier menarche that acts in parallel with the increasing age of the woman. Calculation of sex ratio demonstrated a tendency towards female offspring close to the age at menarche of 12 years. Age at menarche could serve as a surrogate parameter for reproductive potential towards personalized management of infertility.

First trimester neutrophil-to-lymphocyte ratio (NLR) and pregnancy outcomes in medically assisted reproduction (MAR): a case control study.

As success rates after medically assisted reproduction (MAR) technologies have remained constantly limited during the last years, there has been a systematic effort to predict clinical outcomes. There is currently weak evidence to name the neutrophil-to-lymphocyte ratio (NLR), as an accurate predictor in MAR. Through a case control study, and by setting strict eligibility criteria, we enrolled 66 women (35 with negative outcome and 31 cycles with live birth), in terms of NLR at the time of oocyte retrieval. Clinical and IVF cycle characteristics were comparable in a normalized population. There was a positive correlation between NLR and the age of the woman (r = 0.310, p=.011 and rs =0.363, p=.033). Higher odds ratios (ORs) of MAR positive outcome were detected only at higher NLR values, when NLR was divided into quartiles, but only in the 4th quartile [OR =4.33 (95%CI: 1.02-10.79)]. ROC curve resulted on an AUC equal to 0.660 (95%CI: 0.529-0.791) and p value .025. The estimated specificity, sensitivity and cutoff point were 0.57, 0.548, and 1.98, respectively, while PPV and NPV values were 70.6% and 59.3%, respectively. In conclusion, NLR was positively correlated with maternal age; in our study cohort, MAR failure was associated with lower NLR values.

Administration of prednisolone and low molecular weight heparin in patients with repeated implantation failures: a cohort study.

Conflicting results exist for low molecular weight heparin (LMWH) and prednisolone when tested as separate adjuncts for the improvement of the clinical outcomes in patients with repeated implantation failures (RIF) undergoing IVF/ICSI treatment. Through a cohort study, we evaluated the combined effect of both drugs on pregnancy parameters in 115 women with RIF. Clinical pregnancy rate was the primary end point while the sample size was calculated through the results of a pilot study. Clinical and IVF cycle characteristics were also compared between the groups. Baseline and cycle characteristics were comparable between groups. Biochemical and clinical pregnancy rates were similar in both groups [23/57 (40.4%) vs. 14/58 (24.1%), and 17/57 (29.8%) vs. 11/58 (19%), p = .063, and .175, respectively]. Similarly, miscarriage rates were comparable between the groups (35.7% vs. 34.8%), as well as live birth rates [15/57 (26.3%) vs. 9/58 (15.5%), p = .154]. In conclusion, the administration of LMWH with prednizolone in subfertile women with RIF seems not to improve clinical pregnancy rates, but a full-scaled RCT would definitely be more accurate.

Mild versus conventional antagonist ovarian stimulation protocols in expected normal responders undergoing IVF/ICSI: a case-control study.

Mild controlled ovarian hyperstimulation (COH) protocols combining clomiphene citrate (CC) or letrozole with gonadotropins were introduced as an effective alternative of conventional COH in normal responders undergoing IVF/ICSI. In this case-control study, we compared 41 participants treated with a mild stimulation protocol receiving gonadotropins combined with either CC (n = 24) or letrozole (n = 17) with 71 subfertile participants with matching baseline characteristics, conforming with the same inclusion criteria and treated with a conventional antagonist protocol. Live birth was determined in reduced rates in the study group compared to the control group, reaching marginal statistical significance [4/41 versus 19/71, p = 0.050], as also in the respective number of clinical pregnancies [6/41 versus 22/71, p = 0.054], although the incidence of miscarriage was similar for both groups [2/41 versus 5/71, p = 0.714]. Most of the secondary parameters examined, favored the conventional antagonist protocol. There was no difference in any of the outcomes reported between the three different stimulation groups in post-hoc analysis. Mild stimulation regimens with the aid of either CC or letrozole employing GnRH antagonists do not seem to constitute an equally effective method as compared to the conventional antagonist protocol to be offered in good prognosis subfertile women seeking an induced cycle toward IVF/ICSI.

Oocyte Maturation and miRNAs: Studying a Complicate Interaction to Reveal Possible Biomarkers for Female Infertility.

Cellular metabolism, apoptosis, fertilization, and proliferation of granulosa cells belong to a battery of processes where microRNAs can be detected and associated with infertility. The aim of the present review is to focus on mammalian oocyte maturation events and the association between oocyte growth and miRNA expression. PubMed/Medline, Google Scholar and Scopus databases were searched, and 33 studies were included. Regarding the correlation among miRNA expression and the regulation of granulosa cells and cumulus cells, the most important miRNAs were let-7b, let-7c and miR-21. Additionally, the loss of Dicer, an enzyme involved in miRNA biogenesis, is probably a crucial factor in oogenesis, oocyte maturation and embryogenesis. Furthermore, miRNAs interfere with different cellular mechanisms like apoptosis, steroidogenesis, genome integrity, angiogenesis, antioxidative response and, consequently, oocyte maturation. Hence, it is of major importance to clarify the role and mechanism of each miRNA as understanding its action may develop new tools and establish new diagnostic and treatment approaches for infertility and ovarian disorders.

Comparison of Two Different Sedation Protocols during Transvaginal Oocyte Retrieval: Effects on Propofol Consumption and IVF Outcome: A Prospective Cohort Study.

(1) Background: There has been various reports on the potential impact of anesthetic agents used during oocyte retrieval (OR) on the impairment of the capacity of the oocyte for fertilization and subsequent embryo quality; results have been conflicting; (2) Methods: The effects of two different sedation protocols during OR in two groups of patients undergoing In Vitro Fertilization/Intra-Cytoplasmic Sperm Injection IVF/ICSI, were compared on propofol consumption and on in vitro fertilization (IVF)/ICSI success. The study group received dexmedetomidine and fentanyl, while the control remifentanil and midazolam. In a prospective cohort study, we encompassed 72 cycles/patients. The administered dose of propofol per patient and fertilization rates were the primary outcomes, while anesthesiological parameters and IVF/ICSI outcomes were the secondary endpoints; (3) Results: We found a significant increase in propofol consumption in the study compared to the control group (77.0 ± 10.6 mg vs. 12.1 ± 6.1; p < 0.001), but fertilization rates were similar (p = 0.469). From the secondary anesthesiological outcomes, the post anesthesia discharge scores were better in the control group (15.0 (13.5 min) vs. 5.0 (10.0 min), p = 0.028). From the IVF/ICSI secondary outcome parameters, we found a higher quality of embryos on day three in the study compared to the control group (p = 0.040). The comparison of the other secondary outcomes yielded non-significant differences; (4) Conclusions: The use of dexmedetomidine, as an alternative agent during OR, was associated with higher propofol consumption as a rescue dose compared to remifentanil but was linked with similar fertilization rates and higher quality of embryos produced.

Estradiol Pretreatment in an Ultrashort GnRH Combined with a GnRH Antagonist Protocol in A Cohort of Poor Responders Undergoing IVF/ICSI: A Case-control Study.

AIM: To provide results of the use of estradiol pretreatment in a combination of an ultrashort gonadotropin-releasing hormone (GnRH) agonist and antagonist protocol, in an attempt to improve the clinical outcomes in "poor responders", according to the Bologna criteria, undergoing in vitro fertilization (IVF). PATIENTS AND METHODS: We applied estradiol pretreatment to 20 participants before the initiation of a combination of an ultrashort GnRH agonist plus an GnRH antagonist protocol followed by high doses of gonadotropins; the control group consisted of 20 subfertile participants with matching age, body mass index (BMI), basal follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), antral follicle count (AFC) and cause of subfertility, conforming with the same inclusion criteria and treated with a fixed GnRH antagonist protocol. The primary outcome measure was live birth, while the secondary outcomes included embryological and cycle parameters. RESULTS: Live birth was determined in reduced rates in the study compared to the control group (0/20 vs. 3/20, p=0.231) as also in the respective number of clinical pregnancies (2/20 vs. 5/20, p=0.407) and cancellations (10/20 vs. 6/20, p=0.197), but none of these differences reached statistical significance. Also, most of the secondary parameters studied were similar for both groups. CONCLUSION: The study protocol does not seem to constitute an equally effective method compared to the GnRH antagonist protocol in the selected study population. The presented dissimilar results with those reported so far in the literature are possibly attributed to the small sample size and the strict criteria applied when labeling participants as "poor responders".