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The aim of this study was to investigate the relationship between normal Fragile X mental retardation gene 1 (FMR1) CGG repeat numbers and primary ovarian insufficiency (POI) occurrence or subsequent resumption of ovarian function. A total of 122 women with POI and 105 controls were followed up and analysed in our centre. The prevalence of premutation and intermediate range of FMR1 CGG repeats in Han Chinese women with POI was only 0.81% (1/122) and 1.64% (2/122), respectively. The risk of POI occurrence for less than 26 CGG repeats and 29 or more CGG repeats in allele1 (smaller allele) was significantly higher than that for 26-28 CGG repeats (odds ratio 13.50, 95% confidence interval: 3.21 to 56.77 and 6.32, 95% confidence interval: 2.49 to 16.09 respectively; both P < 0.001). No significant difference was found in the CGG repeat distribution (

// Shengli Lin 1, * , Rui Yang 1, * , Hongbin Chi 1 , Ying Lian 1 , Jiejing Wang 1 , Shuo Huang 1 , Cuiling Lu 1 , Ping Liu 1 , Jie Qiao 1 1 Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China * These authors have contributed equally to this work Correspondence to: Ping Liu, email: bysylp@sina.com Keywords: IVF, decreased ovarian reserve, ectopic pregnancy Received: November 04, 2016 Accepted: January 09, 2017 Published: January 16, 2017 ABSTRACT The incidence of ectopic pregnancy after assisted reproductive technology is increased approximately 2.5–5-fold compared with natural conceptions. Strategies were used to decrease the incidence of ectopic pregnancy, but ectopic pregnancy still occurs. In the present study, women were selected with decreased ovarian reserve (defined as FSH > 10 IU/L) aged 20 to 38 years who underwent IVF-ET between 2009 and 2014. These 2,061 women were age-matched with an equal number of women with normal ovarian reserve (defined as FSH ≤ 10 IU/L). During cycles following fresh embryo transfer, 93 patients were diagnosed with ectopic pregnancy. The incidence of ectopic pregnancy in clinical pregnancies was significantly higher in the decreased ovarian reserve than in the normal ovarian reserve group (5.51% vs. 2.99%). After adjusting for confounding factors, the incidence of ectopic pregnancy was significantly associated with decreased ovarian reserve. Our results showed that decreased ovarian reserve is an independent risk factor for ectopic pregnancy after in vitro fertilization-embryo transfer.

STUDY QUESTION Could in vitro maturation (IVM) following transvaginal oocyte retrieval during gynaecological surgery (IVM-surgery) be an effective and safe strategy for fertility preservation? SUMMARY ANSWER IVM-surgery on unstimulated ovaries is a novel option that can be considered for fertility preservation for women requiring gynaecological surgery, but more research is needed to identify appropriate patients who may benefit and to determine the cost-effectiveness of such an approach. WHAT IS KNOWN ALREADY IVM followed by oocyte/embryo cryopreservation has been useful as a safe reproductive strategy for some infertile women. STUDY DESIGN, SIZE, DURATION This prospective cohort study comprised 158 consecutive women with polycystic ovary syndrome (PCOS) who underwent laparoscopy or hysteroscopy for other reasons and had concomitant transvaginal oocyte retrieval followed by IVM between 2014 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 158 women with anovulatory PCOS who underwent IVM-surgery in our infertility centre were recruited for this study. Matured IVM oocytes obtained from these women were either freshly fertilized and subsequently frozen at the blastocyst stage (fresh oocyte group, n = 46) or the oocytes were frozen (frozen oocyte group, n = 112) for fertility preservation followed by later thawing for insemination and cleavage embryo transfer (ET) (n = 33). The following outcomes were then evaluated: embryological data, clinical pregnancy rate, live birth rate (LBR), neonatal outcomes, post-operative complications and post-operative ovarian function. MAIN RESULTS AND THE ROLE OF CHANCE Among all the women who underwent IVM-surgery, the clinical pregnancy rate and LBR per initiated IVM cycle were 9.5% (15/158) and 6.9% (11/158), respectively. Women (40.6%, 20/33) who underwent the procedure with frozen-thawed oocytes (oocyte survival rate, 83.0%) obtained a high quality of cleaved embryos. In the fresh oocyte group, the clinical pregnancy rate and LBR per ET cycle were 69.2 and 53.8%, respectively. In the frozen oocyte group, the clinical pregnancy rate and LBR per ET cycle were 28.6 and 19.1%, respectively. No adverse neonatal outcomes were recorded. IVM-surgery was not associated with post-operative complications, a longer hospital stay, or impaired ovarian function. LIMITATIONS, REASONS FOR CAUTION Because of the small sample size and the low utilization rate and cost-effectiveness per retrieval, the present findings should be interpreted with caution, and further studies are needed for the long-term follow-up of live births. WIDER IMPLICATIONS OF THE FINDINGS This strategy can also help patients with normal ovulation to obtain available oocytes and embryos for cryopreservation and subsequent use. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Joint Research Fund for Overseas Natural Science of China (No. 31429004), the National Key Research and Development Program of China (No. 2017YFC1002000, 2017YFC1001504, 2016YFC1000302), the Ministry of Science and Technology of China Grants (No. 2014CB943203), the Chinese Society of Reproductive Medicine Fund (No. 16020400656) and the National Natural Science Foundation of China (No. 81300456). All the authors have nothing to disclose in terms of conflicts of interest. TRIAL REGISTRATION NUMBER chictr-ONC-17011861

Background Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. Methods This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age

STUDY QUESTION What is the effect of basic fibroblast growth factor (bFGF) on the growth of individual early human follicles in a three-dimensional (3D) culture system in vitro? SUMMARY ANSWER The addition of 200 ng bFGF/ml improves human early follicle growth, survival and viability during growth in vitro. WHAT IS KNOWN ALREADY It has been demonstrated that bFGF enhances primordial follicle development in human ovarian tissue culture. However, the growth and survival of individual early follicles in encapsulated 3D culture have not been reported. STUDY DESIGN, SIZE, DURATION The maturation in vitro of human ovarian follicles was investigated. Ovarian tissue (n= 11) was obtained from 11 women during laparoscopic surgery for gynecological disease, after obtaining written informed consent. One hundred and fifty-four early follicles were isolated by enzymic digestion and mechanical disruption. They were individually encapsulated into alginate (1% w/v) and randomly assigned to be cultured with 0, 100, 200 or 300 ng bFGF/ml for 8 days. PARTICIPANTS/MATERIALS, SETTING, METHODS Individual follicles were cultured in minimum essential medium α (αMEM) supplemented with bFGF. Follicle survival and growth were assessed by microscopy. Follicle viability was evaluated under confocal laser scanning microscope following Calcein-AM and Ethidium homodimer-I (Ca-AM/EthD-I) staining. MAIN RESULTS AND THE ROLE OF CHANCE After 8 days in culture, all 154 follicles had increased in size. The diameter and survival rate of the follicles and the percentage with good viability were significantly higher in the group cultured with 200 ng bFGF/ml than in the group without bFGF (P < 0.05). The percentage of follicles in the pre-antral stage was significantly higher in the 200 ng bFGF/ml group than in the group without bFGF (P < 0.05), while the percentages of primordial and primary follicles were significantly lower (P < 0.05). LIMITATIONS, REASONS FOR CAUTION The study focuses on the effect of bFGF on the development of individual human early follicles in 3D culture in vitro and has limited ability to reveal the specific effect of bFGF at each different stage. The findings highlight the need to improve the acquisition and isolation of human ovarian follicles. WIDER IMPLICATIONS OF THE FINDINGS The in vitro 3D culture of human follicles with appropriate dosage of bFGF offers an effective method to investigate their development. Moreover, it allows early follicles to be cultured to an advanced stage and therefore has the potential to become an important source of mature oocytes for assisted reproductive technology; particularly as an option for fertility preservation in women, including patients with cancer. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Basic Research Program of China (2011|CB944504, 2011CB944503) and the National Natural Science Foundation of China (81200470, 81000275, 31230047, 8110197). There are no conflicts of interest to declare.

Spontaneous 46,XX primary ovarian insufficiency (POI), also known as ‘premature menopause’ or ‘premature ovarian failure’, refers to ovarian dysfunction that results in a range of abnormalities, from infertility to early menopause as the end stage. The most common known genetic cause of POI is the expansion of a CGG repeat to 55–199 copies (premutation) in the 5′ untranslated region in the X-linked fragile X mental retardation 1 (FMR1) gene. POI associated with the FMR1 premutation is referred to as fragile X-associated POI (FXPOI). Here, we characterize a mouse model carrying the human FMR1 premutation allele and show that FMR1 premutation RNA can cause a reduction in the number of growing follicles in ovaries and is sufficient to impair female fertility. Alterations in selective serum hormone levels, including FSH, LH and 17β-estradiol, are seen in this mouse model, which mimics findings in humans. In addition, we also find that LH-induced ovulation-related gene expression is specifically altered. Finally, we show that the FMR1 premutation allele can lead to reduced phosphorylation of Akt and mTOR proteins. These results together suggest that FMR1 premutation RNA could cause the POI associated with FMR1 premutation carriers, and the Akt/mTOR pathway may serve as a therapeutic target for FXPOI.

Primary ovarian insufficiency (POI), also known as premature ovarian failure (POF), is defined as more than six months of cessation of menses before the age of 40 years, with two serum follicle stimulating hormone (FSH) levels (at least 1 month apart) falling in the menopause range. The cause of POI remains undetermined in the majority of cases, although some studies have reported increased levels of reactive oxygen species (ROS) in idiopathic POF. The role of mitochondrial DNA in the pathogenesis of POI has not been studied extensively. This aim of this study was to uncover underlying mitochondrial genetic defects in patients with POI. The entire region of the mitochondrial genome was amplified in subjects with idiopathic POI (n=63) and age-matched healthy female controls (n=63) using nine pair sets of primers, followed by screening of the mitochondrial genome using an Illumina MiSeq. We identified a total of 96 non-synonymous mitochondrial variations in POI patients and 93 non-synonymous variations in control subjects. Of these, 21 (9 in POI and 12 in control) non-synonymous variations had not been reported previously. Eight mitochondrial cytochrome coxidase 1 (MT-CO1) missense variants were identified in POI patients, whereas only four missense mutations were observed in controls. A high incidence of MT-CO1 missense variants were identified in POI patients compared with controls, and the difference between the groups was statistically significant (13/63 vs. 5/63, p=0.042). Our results show that patients with primary ovarian insufficiency exhibit an increased incidence of mitochondrial cytochrome c oxidase 1 gene mutations, suggesting that MT-CO1 gene mutation may be causal in POI.

Gonadotropins have been widely used in human-assisted reproduction and animal science for the past four decades. However, the effects of gonadotropins on oocyte maturation at the molecular and biochemical levels are poorly understood. To determine the effects of gonadotropins (recombinant follicle stimulating hormone and urinary human menopausal gonadotropin) on oocyte maturation, we used the bovine oocyte in vitro maturation model. First, we studied the effects of increasing gonadotropin concentrations on nuclear maturation and mitochondrial function in oocytes. Gonadotropins at concentrations of 0.075 and 0.75 IU/ml improved nuclear maturation and increased inner mitochondrial membrane potential and ATP levels; however, there were no beneficial effects at concentrations of 7.5 and 75 IU/ml. Second, we studied the effects of increasing gonadotropin concentrations on the status of methylation in matured (MII) oocytes. Aberrant methylation and demethylation of H19, SNRPN, and PEG3 genes were observed in MII oocytes at all concentrations except 0.075 IU/ml. The expression of genes that function in spindle formation, cell cycle control, and methylation was also downregulated by high gonadotropin concentrations. In conclusion, we established the optimal gonadotropin concentration (i.e., 0.075 IU/ml) to be used for bovine oocyte in vitro maturation studies. These results may provide a guide for clinical stimulation protocols and help to reduce the risks associated with gonadotropin administration during in vitro fertilization treatment.

Background Bronchofiberscopy, a widely used procedure for the diagnosis of various pulmonary diseases within intensive care units, has a history of association with nosocomial infections. Between September and November 2009, an outbreak caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) was observed in the intensive care unit of a tertiary care hospital in Beijing, China. This study is aimed to describe the course and control of this outbreak and investigate the related risk factors. Methods Clinical and environmental sampling, genotyping with repetitive extragenic palindromic polymerase chain reaction (REP-PCR), and case–control risk factor analysis were performed in the current study. Results During the epidemic period, 12 patients were infected or colonized with MDR-Ab. Sixteen (72.7%) of twenty-two MDR-Ab isolates from the 12 patients and 22 (84.6%) of 26 MDR-Ab isolates from the bronchofiberscope and the healthcare-associated environment were clustered significantly into a major clone (outbreak MDR-Ab strain) by REP-PCR typing. Seven patients carrying the outbreak MDR-Ab strain were defined as the cases. Six of the seven cases (83%) received bronchofiberscopy versus four of the 19 controls (21%) (odds ratio, 22.5; 95% confidence interval, 2.07–244.84; P = 0.005). Several potential administrative and technical problems existed in bronchofiberscope reprocessing. Conclusions Bronchofiberscopy was associated with this MDR-Ab outbreak. Infection control precautions including appropriate bronchofiberscope reprocessing and environmental decontamination should be strengthened.