Exome-based genome-wide screening of rare variants associated with the risk of polycystic ovary syndrome.

Purpose: Genetic factors associated with the risk of polycystic ovary syndrome (PCOS) remain largely unknown. Here, we conducted an optimal sequence kernel association test (SKAT-O), an exome-based rare variant association study, to clarify whether rare variants in specific genes contribute to the development of PCOS. Methods: SKAT-O was performed using exome data of 44 Japanese patients with PCOS and 301 control women. We analyzed frequencies of rare probably damaging variants in the genome. Results: Rare variants of GSTO2 were more commonly identified in the patient group than in the control group (6/44 vs. 1/301; Bonferroni-corrected p-value, 0.028), while the frequencies of variants in other genes were comparable between the two groups. The identified GSTO2 variants were predicted to affect the function, structure, stability, hydrophobicity, and/or the formation of intrinsically disordered regions of the protein. GSTO2 encodes a glutathione transferase that mediates the oxidative stress response and arsenic metabolism. Previously, common variants in GSTO2 and its paralog GSTO1 were associated with the risk of PCOS. Conclusions: The results indicate that there are no genes whose rare variants account for a large fraction of the etiology of PCOS, although rare damaging variants in GSTO2 may constitute a risk factor in some cases.

Ovulation patterns affect the offspring sex ratios and change with the women's age.

BACKGROUND: The aim of this study was to evaluate whether women's ages at conception and the ratio of male to female infants are associated with various ovulation patterns. METHODS: An observational clinical study was conducted in private OB/GYN clinics. Infertile women with regular menstrual cycles receiving intrauterine insemination (IUI) and/or in-vitro fertilization (IVF) had their ovulation patterns monitored in three consecutive spontaneous cycles receiving infertility treatment in the third cycle. Ovulation patterns were also observed in women with slight ovulation disorders during IUI and/or IVF in clomiphene citrate stimulated cycles. All the pregnant women's ages at conception and their respective offspring sex ratios were compared to various ovulation patterns. Statistical evaluation was performed using ANOVA, unpaired t test, χ2 test or Fisher's exact test, heterogeneity χ2 test, odds ratios at 95% confidence intervals and logistic regression. RESULTS: Contralateral ovulation (i.e. ovulation jumping from ovary to the other) was more often observed in relatively younger women, who showed a higher probability of having a boy than after ipsilateral ovulation. There was a significantly higher frequency of boys being conceived following three consecutive ovulations with a left-left-right (LLR) ovulation pattern, while three ovulations from the left ovary (LLL) were associated with a higher frequency of girls. We also found two consecutive menstrual cycles the left-right (LR) ovulation pattern showed a similar significant difference compared to the left-left (LL) ovulation. Both the infertile and infertile + fertile women groups showing right-sided ovulation, regardless of age, showed significantly higher offspring sex ratio compared to left-sided ovulation, which was not observed in the group of fertile women alone. CONCLUSIONS: LLR, LR and contralateral ovulation happens more often in younger women and favors male offspring in infertile women. Right-sided ovulation favors male offspring in infertile and infertile + fertile women, which was not observed in the group of fertile women.

It is of interest to evaluate whether ovulation patterns change with women's ages at conception and affect offspring sex ratios. An observational clinical study was conducted in private OB/GYN clinics. Infertile women with regular menstrual cycles receiving intrauterine insemination (IUI) and/or in-vitro fertilization (IVF) had their ovulation patterns monitored in three consecutive spontaneous cycles receiving infertility treatment in the third cycle. Ovulation patterns were also observed in women with slight ovulation disorder during IUI and/or IVF in clomiphene citrate stimulated cycles. Women's ages and offspring sex ratios were compared to various ovulation patterns. The contralateral ovulation was more often observed in relatively younger women, who showed a higher probability of having a boy than following a pregnancy after ipsilateral ovulation. There was a significantly higher frequency of boys being conceived following three consecutive ovulations with after a left-left-right (LLR) ovulation pattern, while three ovulations from the left ovary (LLL) were associated with a higher frequency of girls. Only considering two consecutive menstrual cycles the left-right (LR) ovulation pattern showed a similar significant difference compared to the left-left (LL) ovulation. Both infertile and infertile + fertile women showing right-sided ovulation, regardless of age, showed significantly higher offspring sex ratio compared to left-sided ovulation, which was not observed in the group of fertile women alone. LLR, LR and contralateral ovulation happens more often in younger women and favor male offspring in infertile women. Right-sided ovulation favors male offspring in infertile and infertile + fertile women, which was not observed in the group of fertile women.

Prediction of plant-level tomato biomass and yield using machine learning with unmanned aerial vehicle imagery.

BACKGROUND: The objective of this study is twofold. First, ascertain the important variables that predict tomato yields from plant height (PH) and vegetation index (VI) maps. The maps were derived from images taken by unmanned aerial vehicles (UAVs). Second, examine the accuracy of predictions of tomato fresh shoot masses (SM), fruit weights (FW), and the number of fruits (FN) from multiple machine learning algorithms using selected variable sets. To realize our objective, ultra-high-resolution RGB and multispectral images were collected by a UAV on ten days in 2020's tomato growing season. From these images, 756 total variables, including first- (e.g., average, standard deviation, skewness, range, and maximum) and second-order (e.g., gray-level co-occurrence matrix features and growth rates of PH and VIs) statistics for each plant, were extracted. Several selection algorithms (i.e., Boruta, DALEX, genetic algorithm, least absolute shrinkage and selection operator, and recursive feature elimination) were used to select the variable sets useful for predicting SM, FW, and FN. Random forests, ridge regressions, and support vector machines were used to predict the yield using the top five selected variable sets. RESULTS: First-order statistics of PH and VIs collected during the early to mid-fruit formation periods, about one month prior to harvest, were important variables for predicting SM. Similar to the case for SM, variables collected approximately one month prior to harvest were important for predicting FW and FN. Furthermore, variables related to PH were unimportant for prediction. Compared with predictions obtained using only first-order statistics, those obtained using the second-order statistics of VIs were more accurate for FW and FN. The prediction accuracy of SM, FW, and FN by models constructed from all variables (rRMSE = 8.8-28.1%) was better than that from first-order statistics (rRMSE = 10.0-50.1%). CONCLUSIONS: In addition to basic statistics (e.g., average and standard deviation), we derived second-order statistics of PH and VIs at the plant level using the ultra-high resolution UAV images. Our findings indicated that our variable selection method reduced the number variables needed for tomato yield prediction, improving the efficiency of phenotypic data collection and assisting with the selection of high-yield lines within breeding programs.

New device for sperm preparation involving migration-gravity sedimentation without centrifugation compared with density-gradient centrifugation for normozoospermic intrauterine insemination.

OBJECTIVE: To investigate the efficacy of a new device for sperm preparation involving migration-gravity sedimentation without centrifugation (MIGLIS), compared with density-gradient centrifugation (DGC) for normozoospermic intrauterine insemination (IUI). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENTS: A total of 10,318 cases of IUI (3,015 MIGLIS and 7,303 DGC) between October 2013 and September 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sperm analysis, subsequent pregnancy outcomes, and complications. RESULTS: MIGLIS was associated with a lower sperm recovery rate and fewer injected sperm compared with DGC. However, the overall pregnancy rates following MIGLIS and DGC were similar (MIGLIS 8.8%, DGC 9.3%). In a subanalysis according to age, the pregnancy rate was higher for MIGLIS among women 40-41 years of age (8.6% vs. 5.9%). Peritonitis was the only recorded complication, with similar frequencies in the MIGLIS and DGC groups (MIGLIS two cases, DGC four cases). No cases became severe, and all improved after antibiotic treatment. There were no cases of uterine cramping or pain symptoms. CONCLUSIONS: MIGLIS is a new sperm preparation method that does not require centrifugation. Its use was associated with pregnancy rates similar to those with DGC and a higher pregnancy rate in older women. MIGLIS is a novel sperm preparation method for selecting spermatozoa with high motility and good fertilization ability in patients undergoing IUI, in vitro fertilization, and intracytoplasmic sperm injection.

Effects of ozone on the growth and yield of rice (Oryza sativa L.) under different nitrogen fertilization regimes.

To examine whether the sensitivity of growth and yield of rice (Oryza sativa L.) to ozone (O3) varies under different nitrogen (N) fertilization conditions, rice cultivar 'Koshihikari' was exposed to O3 under either standard N (SN) fertilization or no N (NN) fertilization. The rice plants were subjected to three gas treatments (charcoal-filtered air (CF) and O3 at 1.0 (1.0×O3) and 1.5 (1.5×O3) times the ambient concentration) in combination with two conditions of N fertilization. At five time points throughout the growth period, plant samples were collected to measure the leaf area and dry mass of each plant organ. At the final harvest, yield, yield components, and harvest index were measured. There was a significant interactive effect of O3 and N on leaf, stem, root, and whole-plant dry mass at the final harvest. The dry mass of each plant organ and the whole-plant dry mass of rice plants grown in 1.5×O3 were significantly lower than those in the plants grown in CF and 1.0×O3 under SN, whereas there were no significant differences in the dry mass among the three gas treatments under NN. Brown rice yield was significantly reduced by the exposure to O3 under SN, but not under NN. Relative yield loss rate based on the AOT40 (accumulated exposure over a threshold of 40 nmol mol-1) was pronounced under SN, whereas relative yield was almost unchanged at different AOT40 levels under NN. We concluded that the sensitivity of growth and yield of rice to O3 is dependent on N levels in the soil; the exposure to ambient levels of O3 has a negative effect on rice under SN, but not under NN.

Acceptable pregnancy rate of unstimulated intrauterine insemination: a retrospective analysis of 17,830 cycles.

PURPOSE: To evaluate the pregnancy rate (PR) of unstimulated intrauterine insemination (IUI). METHODS: This was a retrospective study in a private fertility clinic. Between 2004 and 2013, a total of 4,045 women underwent 17,830 cycles of unstimulated IUI. The etiologies of subfertility in the couples were unexplained (51 %), male factor (36 %), coital problems (9.5 %), and cervical factor (3.5 %). RESULTS: The PRs/cycle, between the 1st and 9th trials, in women <35, 35-37, 38-40, 41-42, and >42 years of age were 8.2, 7.3, 5.5, 3.6, and 0.9 %, respectively. In 10,076 cycles in which the male partner had a total motile sperm count ≥5 million, the PRs in the respective age groups were 9.9, 8.6, 6.1, 4.8, and 1.2 %. The largest-sized reported PRs for clomiphene citrate (CC)/IUI in the respective age groups were 11.5, 9.2, 7.3 4.3, and 1.0 % (4,199 cycles in total, Dovey et al., FertilSteril, 2008;90:2281-2286). There were no significant differences in PRs between unstimulated IUI and CC/IUI. CONCLUSION: PR for unstimulated IUI was similar to the reported PR for CC/IUI. Although this was a retrospective study without a control group, to reduce multiple pregnancy rate, we believe that unstimulated IUI is a reasonable treatment.

A questionnaire-based survey to assess patient satisfaction, ease-of-learning, ease-of-use, injection site pain and overall patient satisfaction of the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen compared with other systems of gonadotrophin administration.

BACKGROUND: Gonadotrophins are used routinely for follicular stimulation during ovarian induction and assisted reproduction techniques. Developments in recombinant follicle-stimulating hormone preparations and their injection devices have improved patient quality of life by enabling patients to self-administer treatment at home. The objective of this study was to investigate patient experiences of learning to use and overall satisfaction with the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen. METHODS: This questionnaire-based survey study was conducted in 23 fertility centres in Japan over a period of 14 months. Patients who were receiving fertility treatment with the follitropin-alpha (FbM) prefilled pen were asked to complete a questionnaire to assess their satisfaction, ease of learning and use, and injection site pain following treatment. RESULTS: A total of 663 women participated in the study. The majority of patients found the instructions for administering follitropin-alpha with the prefilled pen easy to understand (83.0%; n = 546/658) and patients found that a hands-on demonstration by a nurse or doctor was the most useful tool for learning to use the follitropin-alpha (FbM) prefilled pen (80.0%; n = 497/621). Forty-eight percent (n = 318) of patients in the study had previous experience with different types of fertility medications and the majority of these patients found the follitropin-alpha (FbM) prefilled pen easier to use (75.1%; n = 232/309) and less painful (89.0%; n = 347/390) than their previous medication. The majority (80.2%; n = 521/650) of patients reported overall satisfaction with the follitropin-alpha (FbM) prefilled pen. CONCLUSIONS: The follitropin-alpha (FbM) prefilled pen is an easy-to-use injection device according to this questionnaire-based survey. Patients who had experience of different types of fertility medication preferred the follitropin-alpha (FbM) prefilled pen to other injection devices.

The ovulation pattern during three consecutive menstrual cycles has a significant impact on pregnancy rate and sex of the offspring.

Identification of the ovary at the time of ovulation during three consecutive menstrual cycles results in one of eight ovulation patterns, left-left-right, right-left-right, left-right-right, and right-right-right of right-sided ovulation and right-right-left, left-right-left, right-left-left, and left-left-left of left-sided ovulation. Our data suggest that IVF and IUI treatment in cycles in which development of the preovulatory follicle(s) occurs in the right-sided ovary-and ovulations took place from the left-sided ovary in the preceding two cycles (left-left-right)-is likely to show the best pregnancy potential and high offspring sex ratio.