Menarche is a major biologic event associated with women's health through the lifespan. Social and economic deprivation is known to be related with delayed menarche. We explored the association between delayed menarche and deprivation index of the school area. Retrospective cohort study. A total of 187,024 female middle- and high-school students in the Korea Youth Risk Behavior Web-based Survey (KYRBS) from 2006 to 2015 were analyzed. Delayed menarche was defined as absence of menarche by 14 years of age. Area-level deprivation index where the school located were calculated using 2010 Korean Census data. We conducted regression analyses including body mass index (BMI), father's and mother's education, absence of one of the parents, year of survey and birth cohort (1988-1992, 1993-1997, 1998-2003) to calculate the odds ratio (OR) for delayed menarche. Delayed menarche occurred in 6.5% in the study population. The birth year-specific prevalence decreased from 8.3% (236/2,950) in girls born in 1988 to 3.8% (210/1,076) in those born in 1999. When the population was divided into 4 groups by deprivation index quartiles, late menarche occurred in 6.0% (least deprived), 6.1%, 6.5%, and 6.7% (most deprived) of each group. In the multivariable regression model, girls going to school in area with upper 3rd (1.11, 95% CI: 1.02, 1.21) and 4th quartiles (1.16, 95% CI: 1.07, 1.25) of deprivation index had higher risk for late menarche. This study suggests going to school located in more deprived area is associated with higher odds for delayed menarche. Future studies of timing of menarche would need to consider the potential effect of area-level deprivation.

Social deprivation has been suggested to be associated with lower success of in-vitro fertilization (IVF) cycles. We were to explore the relationship between area-level deprivation index and probabilities of intrauterine pregnancy in women who underwent one or more IVF cycles. We analyzed 4,581 women who had underwent one or more fresh IVF cycles at a single IVF center from January 2006 to December 2014 and lived in Seoul at the time of IVF treatment. District-level deprivation index calculated using 2010 Korean Census data were assigned to each individual. We conducted survival analyses for estimating probability of intrauterine pregnancy. Covariates included into the model were women's age, body mass index, number of retrieved oocytes, intracytoplasmic injection, blastocyst transfer, season, and year of IVF treatment. Intrauterine pregnancy rate per cycle was 34.9% and 51.3% per individual. District-level deprivation index was 0.4 on average, ranging from -5.21 (least deprived) to 2.57 (most deprived). When the population was divided into 4 groups by deprivation index quartiles, intrauterine pregnancy occurred in 39.1% (least deprived), 34.1%, 34.8%, and 35.3% (most deprived) of each group (P for trend = 0.973). In multivariable models, the probability for intrauterine pregnancy in IVF cycles was 0.97 (95% CI: 0.87, 1.08) in 2nd, 1.07 (0.96, 1.19) in 3rd , and 0.96 (0.85, 1.09) in 4th quartile of deprivation index compared to lowest quartile group. We found no association between area-level deprivation index of women's residence and probability of successful IVF pregnancy. Future studies exploring environmental factors and IVF pregnancy would better use other index of social deprivation than area-level deprivation index.

To evaluate the association between serum concentration of heavy metals and number of spontaneous abortions in Korean women in the reproductive age. Retrospective cohort study. We analyzed data of women aged 20-49 years and recruited during the sixth Korean National Health and Nutrition Examination Survey 2010-2012 (KNHANES VI). The study population was divided into four groups based on the number of spontaneous abortion (SA) experiences (SA=0, 1, 2, and ≥3). The relationships between serum concentration of each pair of three heavy metals (lead, mercury, and cadmium) and number of spontaneous abortion experiences were calculated using univariable and multivariable models. Covariates included women's age at the time of survey, body mass index, status of alcohol consumption, status of smoking, level of education, and coexistence of chronic diseases. Among a total of 8812 women participants, 6535 were married and with a history of at least one pregnancy. The mean serum lead level was increased with higher number of SA experiences. Increase of serum lead level by one unit increased the risk for SA≥3 (adjusted OR=1.62, 95% CI: 1.06, 2.48) in the multivariable model. In contrast, an inverse relationship was found between cadmium concentration and SA=2 and SA≥3 (OR=0.57 and 0.52, respectively). This relationship was not observed for mercury. The serum lead level is associated with a history of higher number of SAs in women within normal reference. A paradoxical effect of cadmium in early pregnancy was observed. Further studies would be needed to identify potential embryo-toxic effect of lead exposure, which has been presumed to be safe.

Early stage follicle development is far from fully understood. Technical barriers including difficulties in retaining enough human ovarian sample and heterogeneous nature of ovarian tissue which contains various stages of follicles have limited informational accuracy. However recent progression in RNA-Seq has lead to far more precise measurement of levels of transcripts than other methods with less RNA sample. In order to advance our understanding of early folliculogenesis, we performed transcriptomic analysis for isolated human early stage follicle using RNA-Seq. Transcriptomic analysis of isolated human ovarian follicles using high though-put RNA-seq. We isolated primordial (30∼40μm; n=6) and primary (50∼70μm; n=5) follicles enzymatically and mechanically from human ovarian tissue using 1mg/ml collagenase IV, 0.2mg/ml DNase I and 0.08mg/ml Liberase. For this study primordial follicles were defined as those contain flat pregranulosa cells; primary follicles were defined as those with one layer of cuboidal granulosa cells. From total follicles isolated, single follicle from each stage which passed QC were analyzed with RNA-seq (Illumina HiSeq). Transcriptomic analysis revealed 2190 up regulated differentially expressed genes (DEGs) and 1565 down regulated DEGs in primary compared to primordial follicle. Compared to mouse data, 175 upregulated and 218 down regulated common DEGs were found. Gene pathway analysis indicates that these DEGs are involved in signaling pathways such as cell cycle, cancer pathway and phosphorous metabolic process. Our current study provides first RNA-seq based transcriptome between primordial and primary follicle in human. Many candidate genes which have not been studied previously may reveal novel insights into primordial follicle activation and provides a fundamental basis for the future functional studies in early folliculogenesis.