STUDY QUESTIONCan increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)?SUMMARY ANSWERA second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS.WHAT IS KNOWN ALREADYKisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12–14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS.STUDY DESIGN, SIZE, DURATIONPhase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation.PARTICIPANTS/MATERIALS, SETTING, METHODS Study participants: Sixty-two women aged 18–34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence.MAIN RESULTS AND THE ROLE OF CHANCEA second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2–50%, P = 0.042).Patients receiving two doses of kisspeptin-54 had a variable LH-response following the second kisspeptin dose, which appeared to be dependent on the LH-response following the first kisspeptin injection. Patients who had a lower LH-rise following the first dose of kisspeptin had a more substantial ‘rescue’ LH-response following the second dose of kisspeptin. The variable LH-response following the second dose of kisspeptin resulted in a greater proportion of patients achieving an oocyte yield ≥60%, but without also increasing the frequency of ovarian over-response and moderate OHSS (Single: 1/31, 3.2%, Double: 0/31, 0%).LIMITATIONS, REASONS FOR CAUTIONFurther studies are warranted to directly compare kisspeptin-54 to more established triggers of oocyte maturation.WIDER IMPLICATIONS OF THE FINDINGSTriggering final oocyte maturation with kisspeptin is a novel therapeutic option to enable the use of fresh embryo transfer even in the woman at high risk of OHSS.STUDY FUNDING/COMP...

Cryopreservation of oocytes has been proposed as a way of storing gametes in young patients at high risk of infertility and premature ovarian failure. Recent advances in cryobiology have yielded promising results, leading to oocyte cryopreservation becoming a mainstay of fertility preservation. In this case series, we describe the feasibility of performing ovarian stimulation, and the ethical challenges faced, in teenage girls, aged 14-18 years, prior to undergoing bone marrow transplant for sickle cell anaemia. All eight consecutive cases completed ovarian stimulation and oocyte retrieval with mature oocytes being found and cryopreserved for each patient. The mean dose of gonadotrophin stimulation was 2134.38 IU (95% CI 1593.34-2675.4) and the mean duration of treatment was 11 days (95% CI 10.02-11.98). The mean number of oocytes retrieved was 14.88 (95% CI 7.39-22.36), of which a mean of 12.13 (95% CI 4.72-19.54) oocytes were mature and cryopreserved. There was one case of moderate ovarian hyperstimulation syndrome that required hospital admission for supportive treatment. Oocyte cryopreservation is a technique that can be successfully employed after the retrieval of mature oocytes from the peripubertal ovary, restoring hope to these patients, and their families, of having their own genetic children in the future.

Table. Pathological Features and Molecular Profile of Early-Onset Colorectal Cancer Pathological features Molecular profile Poor differentiation Microsatellite stability Mucinous tumors More likely to exhibit LINE-1 hypomethylation and TP53 sequence variations Signet-ring morphology Less frequently harbor KRAS, BRAF V600E, and APC sequence variations Perineural/venous invasion Promoter methylation of CpG islands Abbreviations: APC, adenomatous polyposis coli; BRAF, B-Raf; KRAS, K-Ras; LINE-1, long interspersed nuclear elements; TP53, tumor protein 53.

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Introduction: Polycystic ovarian syndrome (PCOS) is a leading cause of female subfertility worldwide, however due to the heterogeneity of the disorder, the criteria for diagnosis remains subject to conjecture. In the present study, we evaluate the utility of serum Anti-Müllerian hormone (AMH) in the diagnosis of menstrual disturbance due to PCOS.Method: Menstrual cycle length, serum AMH, gonadotropin and sex-hormone levels, total antral follicle count (AFC), body mass index (BMI) and ovarian morphology on ultrasound were analyzed in a cohort of 187 non-obese women, aged 18–35 years, screened for participation in a clinical trial of fertility treatment between 2013 and 2016 at a tertiary reproductive endocrine center.Results: Serum AMH was higher in women with menstrual disturbance when compared to those with regular cycles (65.6 vs. 34.8 pmol/L; P < 0.0001). The odds of menstrual disturbance was increased 28.5-fold (95% CI 3.6–227.3) in women with serum AMH >60 pmol/L, in comparison to those with an AMH < 15 pmol/L. AMH better discriminated women with menstrual disturbance (area under ROC 0.77) from those with regular menstrual cycles than AFC (area under ROC 0.67), however the combination of the two markers increased discrimination than either measure alone (0.83; 95% CI 0.77–0.89). Serum AMH was higher in women with all three cardinal features of PCOS (menstrual disturbance, hyperandrogenism, polycystic ovarian morphology) when compared to women with none of these features (65.6 vs. 14.6 pmol/L; P < 0.0001). The odds of menstrual disturbance were increased by 10.7-fold (95% CI 2.4–47.1) in women with bilateral polycystic morphology ovaries than those with normal ovarian morphology. BMI was a stronger predictor of free androgen index (FAI) than either AMH or AFC.Conclusion: Serum AMH could serve as a useful biomarker to indicate the risk of menstrual disturbance due to PCOS. Women with higher AMH levels had increased rates of menstrual disturbance and an increased number of features of PCOS.