Outdoor air pollution and diminished ovarian reserve among infertile Korean women.

BACKGROUND: Mounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women. METHODS: Our study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting. RESULTS: The mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (ß= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents. CONCLUSIONS: In a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.

Peripheral blood natural killer cell proportion and ovarian function in women with recurrent implantation failure.

Current knowledge of the association between peripheral natural killer (NK) cell proportion and ovarian function in reproductive-age women is limited. We explored the association between NK cell proportion and ovarian function in women who underwent in-vitro fertilization (IVF) treatment. This was a retrospective cohort study using the data of 20-44-year-old women with recurrent implantation failure (RIF) who were tested for NK cell proportion and anti-Müllerian hormone (AMH). Indicators of ovarian function included AMH, observed-to-(age-appropriate) reference AMH ratio, high FSH, peak E2 and total number of oocytes during the first IVF cycle following the test. We used different model specification controlling for women's age, and body mass index. Among a total of 936 women, majority showed lower AMH compared to age-appropriate level. Average NK cell proportion was 13.5 ± 5.7%. Number of oocytes showed positive association with NK cell (ß = 0.040, p = .025). In the subgroup with NK ≥ 18%, NK cell proportion was negatively associated with AMH (-0.106, p = .012), AMH ratio (-0.049, p = .014) and number of oocytes (-0.021, p < .001) while the associations with others remain close to null. High NK cell proportion may be harmful to ovarian reserve or function.

Outcomes of in vitro fertilization cycles following fertility-sparing treatment in stage IA endometrial cancer.

PURPOSE: This study aimed to present cases involving in vitro fertilization (IVF) cycles in patients with stage IA endometrial adenocarcinoma (EC) who underwent fertility-sparing conservative treatment. METHODS: Twenty-two patients who underwent IVF cycles in a single fertility center between May 2005 and February 2017 after progestin treatment for stage IA EC were chosen for this study. Outcomes of IVF cycles were analyzed retrospectively. RESULTS: Women of a median age of 34 years (range 26-41 years) underwent a total of 49 embryo transfers within an average of 2 months after their last progestin treatment. The clinical pregnancy rate per transfer was 26.5%, implantation rate was 16.7%, and live birth rate was 14.3%. The cumulative clinical pregnancy rate was 50% (11/22), resulting in 6 live births (27.3%) within 3 cycles of embryo transfer. The median endometrial thickness on the day of human chorionic gonadotropin injection in 34 fresh cycles was 9.0 mm (range 4-10 mm) in live births, 7.5 mm (range 6-9 mm) in miscarriages, and 6.0 mm (range 4-15 mm) in no pregnancy cases. During a median post-cancer treatment follow-up period of 41 months (range 9-150 months), 6 (27.3%) women underwent definitive hysterectomy for EC relapse. CONCLUSIONS: This study showed an acceptable cumulative pregnancy rate after the IVF procedure in patients with early-stage EC who were treated conservatively. Considering the high relapse rate, it is of great importance that these patients are closely monitored after the IVF cycles.

Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study.

PURPOSE: Supplementation of growth hormone (GH) during controlled ovarian stimulation (COS) has been suggested to improve ovarian response. Despite potential benefits in poor responders, multiple injections of GH during COS are inconvenient. We conducted a randomized controlled study to evaluate the efficacy and safety of sustained-release human GH in poor responders undergoing in vitro fertilization (IVF). METHODS: This was a single-center, randomized, open-label, parallel study. Infertile women who satisfied the Bologna criteria for poor responders were randomized into GH treatment and control groups. The treatment group received a sustained-release GH (Eutropin Plus® 20 mg) three times before and during COS (mid-luteal, late luteal, and menstrual cycle day 2). The baseline characteristics and IVF outcomes were compared between the two groups. RESULTS: A total of 127 patients were included in the analysis. The mean age was 39.6 years and mean anti-Müllerian hormone level was 0.6 ng/ml. There was no significant difference in the baseline characteristics between GH treatment and control groups. The number of follicles on the human chorionic gonadotropin triggering day (3.1 ± 2.3 vs. 2.4 ± 1.6, P = 0.043) and the proportion of metaphase II oocytes (67.5 vs. 52.3%, P = 0.030) were higher in the GH group than in controls. The percentage of clinical and ongoing pregnancy and miscarriage was not different between the two groups. CONCLUSION: Supplementation of sustained-release GH before and during COS improved ovarian response, with an increase in mature oocytes in poor responders. Further studies are needed to ensure this benefit in general infertility patients.

In vitro Fertilization Outcomes of Frozen-thawed Embryo Transfer with Hatched Blastocysts versus with Hatching Blastocysts.

This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.

Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS?

Human pre-ovulatory follicular fluid (FF) contains a higher concentration of melatonin than serum. The aim of this study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcomes of an in-vitro maturation (IVM) IVF-embryo transfer programme for patients with polycystic ovarian syndrome (PCOS). Melatonin concentrations in the culture media of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes after using IVM media with or without melatonin were analysed. In the culture media of GC or COC, melatonin concentrations gradually increased. When human chorionic gonadotrophin priming protocols were used, implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control group (P<0.05). Pregnancy rates were also higher, although not significantly. The findings suggest that the addition of melatonin to IVM media may improve the cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes. It is speculated that follicular melatonin may be released from luteinizing GC during late folliculogenesis and that melatonin supplementation may be used to improve the clinical outcomes of IVM IVF-embryo transfer. Melatonin is primarily produced by the pineal gland and regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. Interestingly, human pre-ovulatory follicular fluid contains a higher concentration of melatonin than serum. However, in contrast to animal studies, the direct role of melatonin on oocyte maturation in the human system has not yet been investigated. So, the aim of the study was to evaluate the effect of melatonin supplementation of culture medium on the clinical outcome of an in-vitro maturation (IVM) IVF-embryo transfer programme for PCOS patients. The melatonin concentrations in culture medium of granulosa cells (GC) or cumulus-oocyte-complexes (COC) were measured and the clinical outcomes of IVM IVF-embryo transfer using IVM medium alone or supplemented with melatonin were analysed. In the culture media of GC or COC, the melatonin concentration gradually increased. With human chorionic gonadotrophin priming, the pregnancy and implantation rates in the melatonin-supplemented group were higher than those of the non-supplemented control (P<0.05). Our findings suggest that follicular melatonin is released from luteinizing GC during late folliculogenesis and plays a positive role in oocyte maturation. Therefore, addition of melatonin into IVM medium may improve cytoplasmic maturation of human immature oocytes and subsequent clinical outcomes.

Combined medroxyprogesterone acetate/levonorgestrel-intrauterine system treatment in young women with early-stage endometrial cancer.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of the combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment in young women with early-stage endometrial cancer who wish to preserve their fertility. STUDY DESIGN: A prospective observational study was conducted. The study population comprised women aged ≤40 years who were diagnosed with endometrioid endometrial cancer, grade 1, tumor size <2 cm presumably confined to the endometrium. A LNG-IUS was inserted in the uterine cavity of each woman, and all of the women received oral MPA (500 mg/d). Dilation was conducted every 3 months. RESULTS: From September 2008 to December 2012, 16 patients were enrolled. The overall complete remission rate was 87.5% (14/16 patients); the average time to complete remission was 9.8 ± 8.9 months (range, 3-35 months). In the initial 3 months of treatment, complete remission was observed in 25% of cases (4/16 patients), partial response in 25% (4/16), and no change in 50% (8/16); there were no cases of progressive disease. Three patients achieved pregnancies. The average follow-up period was 31.1 ± 11.8 months (range, 16-50 months), and there were no treatment-related complications. CONCLUSION: Combined oral MPA/LNG-IUS treatment is considered to be effective and favorable for young patients with early-stage endometrial cancer who want to preserve their fertility.

Correction: Demographic and Clinico-Epidemiological Features of Dengue Fever in Faisalabad, Pakistan.

[This corrects the article DOI: 10.1371/journal.pone.0267652.].

Recombinant human phospholipase C zeta 1 induces intracellular calcium oscillations and oocyte activation in mouse and human oocytes.

BACKGROUND: Oocyte activation is a crucial step that comprises the release of the oocyte from meiotic arrest, pronuclear formation and subsequent embryo development. Oocytes are activated by repetitive increases in the intracellular concentration of free Ca(2+), [Ca(2+)](i) oscillations, which are triggered during fertilization by the introduction of the sperm-specific phospholipase C zeta 1 (PLCZ1). Recent studies have shown that sperm from patients lacking expression of PLCZ1 or expressing mutant forms of PLCZ1 fail to induce [Ca(2+)](i) oscillations or oocyte activation. We first purified recombinant human PLCZ1 (hPLCZ1) protein and evaluated its [Ca(2+)](i) oscillation activity in mouse and human oocytes with the view to investigate its application in the clinic for assisted oocytes activation in lieu of chemical agents. METHODS: Recombinant hPLCZ1 was synthesized using the Escherichia coli system, and subjected to immunoblot analysis with anti-PLCZ1 and anti-His tag antibodies. [Ca(2+)](i) oscillations by microinjection of recombinant hPLCZ1 into mouse or human oocytes were examined by [Ca(2+)](i) monitoring with Fluo 4. Ploidy of the oocytes with recombinant hPLCZ1 injection was confirmed with fluorescence in situ hybridization. RESULTS: A band of 68 kDa on recombinant protein was detected with both antibodies. Injection of recombinant hPLCZ1 induced [Ca(2+)](i) oscillations in a dose-dependent manner in both mouse and human oocytes. These oscillations, which closely resembled those initiated by the sperm upon fertilization, triggered activation and cleavage in oocytes of both species, although further development of the mice embryos was low. U73122, a PLC inhibitor, blocked the ability of hPLCZ1 to initiate oscillations. Microinjection of recombinant hPLCZ1 into ICSI-failed human oocytes rescued fertilization failure in five of eight attempts. CONCLUSIONS: Repeated [Ca(2+)](i) oscillations and oocyte activation were induced in mouse and human oocytes by microinjection of recombinant hPLCZ1 synthesized in E. Coli. Injection of recombinant protein could thus provide a biological solution for inducing artificial activation of oocytes.

High sensitivity C-reactive protein and its relationship with impaired glucose regulation in lean patients with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder, also associated with the metabolic syndrome. Serum high sensitivity C-reactive protein (hs-CRP), a marker of low-grade chronic inflammation is a potent predictor of cardiovascular events, closely linked to metabolic syndrome features and higher in patients with PCOS. However, hs-CRP in lean patients with PCOS has not been fully evaluated and few data are available. We aimed to investigate the relation between glucose intolerance and hs-CRP levels in lean patients with PCOS, and to evaluate the possible relationship between hs-CRP and PCOS by evaluating PCOS-related metabolic abnormalities in Korean women. We consecutively recruited 115 lean (BMI < 25kg/m(2)) patients diagnosed with PCOS and 103 lean healthy controls. The PCOS group was divided two groups: impaired glucose regulation (IGR) and normal glucose tolerance group (NGT). In lean patients with PCOS, hs-CRP level was higher in the IGR group than in the NGT group (0.60 ± 1.37 versus 0.18 ± 0.46, p(Bonf) = 0.023) and other metabolic risk factors were also higher in the IGR group than in the NGT group. And there were close relationships between hs-CRP level and metabolic risk factor, such as 2 h postprandial insulin level in the lean patients with PCOS.

Effect of estrogen priming through luteal phase and stimulation phase in poor responders in in-vitro fertilization.

PURPOSE: To verify whether a novel protocol administering E(2) during the luteal phase of the preceding cycle and during ovarian stimulation in GnRH antagonist cycle could enhance follicular response and hence improve outcomes in poor responders. METHODS: In this retrospective analysis, a total of 155 poor responder patients subjected to IVF/ICSI were analyzed. All the patients had history of more than one prior IVF cycle failure with poor response (less than 5 oocytes retrieved and/or maximal E2 level less than 500 pg/mL) by using conventional long agonist or antagonist protocol. In luteal E2 treatment protocol (n = 86), oral estradiol valerate 4 mg/day was initiated on luteal day 21 and either stopped at menstrual cycle day 3 (Protocol A, n = 28) or continued during the period of ovarian stimulation until the day of hCG injection (Protocol B, n = 58). IVF parameters and pregnancy outcome of luteal E2 treatments group were compared with a standard GnRH antagonist protocol (n = 69) which the patients received no hormonal pretreatment. RESULTS: Compared to standard GnRH antagonist protocol, cancellation rate was lower with luteal E2 group (15.1% vs 37.7%, p < 0.01). Moreover, patients treated with luteal estrogen resulted in an increased number of oocytes retrieved (4.5 ± 2.9 vs 3.2 ± 1.9; p < 0.01). A trend toward increase in number of normally fertilized embryos (2.9 ± 2.1vs 2.3 ± 1.9; p = 0.043), and increased prevalence of good quality embryos (51.2% vs 25%; p = 0.047) were noted. Comparing protocol A and B, there were no significant difference between embryologic data, however there were slight increase in ongoing pregnancy rate in protocol B compared to A (27.1% vs 20%, p = 0.357), although statistical significance was not achieved. CONCLUSION: Estrogen priming through luteal phase and stimulation phase improved ovarian responsiveness and this may lead to an increase in pregnancy rate in poor responders with failed cycle.

Freeze all-first versus biopsy-first: A retrospective analysis of frozen blastocyst transfer cycles with preimplantation genetic testing for aneuploidy.

Potential use of preimplantation genetic testing for aneuploidy (PGT-A) is increasing. Patients who have excess embryos cryopreserved at the blastocyst stage may desire PGT-A but there is little data available on options for these patients. We compared the efficacy and safety of the timing on the cryopreservation and trophectoderm(TE) biopsy for preimplantation genetic testing for aneuploidy (PGT-A) program associated with the better outcomes after frozen blastocyst transfer. Retrospective analysis of patients who underwent PGT-A cycles from January 2016 to December 2019 was carried out. 2684 blastocysts from cycles were subjected to TE biopsy for performing array comparative genomic hybridization test and Next-generation sequencing. All cycles were divided into two according to the timing of biopsy: biopsy-first (n = 211 cases/ 232 transfers) versus freeze all-first (n = 327 cases/ 415 transfers). In the biopsy-first group, embryos were cultured to expanded blastocyst and proceed to TE biopsy on day 5 or day 6 followed by cryopreservation. In the freeze all-first, blastocysts were vitrified and warmed before biopsy. Rates of clinical pregnancy (52.3% vs. 38.7%, P = 0.09) and ongoing pregnancy (44.3% vs. 34.5%, P = 0.07) in biopsy-first were significantly higher than those in freeze all-first. Biopsy-first showed comparable miscarriage rate with freeze all-first (15.2% (33/217) vs.11.1% (10/90), respectively). Rate ratio (RR) for clinical pregnancy was lower in freeze all-first group (adjusted RR = 0.78, 95% confidence interval: 0.65, 0.93). The RRs for miscarriage and live birth was also lower but it did not reach statistical significance. Our result supported performing TE biopsy of blastocyst for PGT-A before vitrification and warming. This finding would contribute to more evidence-based decision in PGT-A cycles.

Use of the natural cycle and vitrification thawed blastocyst transfer results in better in-vitro fertilization outcomes : cycle regimens of vitrification thawed blastocyst transfer.

PURPOSE: To compare the IVF outcomes of vitrification-thawed blastocyst transfer cycles utilizing different endometrial preparation methods. METHODS: We retrospectively assessed IVF outcomes in 611 patients (648 cycles) who underwent blastocyst frozen embryo transfer (FET) between January 2007 and December 2009. All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. Patients were prepared for transfer by using either the natural cycle (n = 310/Group 1), the natural cycle with ovulation induction employing human chorionic gonadotropin (n = 134/Group 2), or a hormonally manipulated artificial cycle with estrogen and progesterone supplementation (n = 204/Group 3). RESULTS: Multivariate logistic regression analysis showed a significant difference in clinical pregnancy rate between Groups 3 (30.4%) and 1 (41.9%) (odds ratio [OR], 0.567; 95% confidence interval [CI], 0.379-0.847, P = 0.006) whereas the difference between Groups 2 and 1 was not significant (41.8% vs. 41.9%; OR, 0.683; 95% CI, 0.435-1.073; P = 0.098). Other significant variables affecting clinical pregnancy rate were the number of embryos transferred, the grade of transferred embryos, and maximal endometrial thickness. CONCLUSION: The results showed that, using vitrification-thawed blastocyst transfer, employment of natural cycles with or without hCG treatment was associated with better outcomes than was the use of hormonally manipulated cycles.

Microtubule Integrity Is Associated with the Functional Activity of Mitochondria in HEK293.

Mitochondria move along the microtubule network and produce bioenergy in the cell. However, there is no report of a relationship between bioenergetic activity of mitochondria and microtubule stability in mammalian cells. This study aimed to investigate this relationship. We treated HEK293 cells with microtubule stabilizers (Taxol and Epothilone D) or a microtubule disturber (vinorelbine), and performed live-cell imaging to determine whether mitochondrial morphology and bioenergetic activity depend on the microtubule status. Treatment with microtubule stabilizers enhanced the staining intensity of microtubules, significantly increased ATP production and the spare respiratory capacity, dramatically increased mitochondrial fusion, and promoted dynamic movement of mitochondria. By contrast, bioenergetic activity of mitochondria was significantly decreased in cells treated with the microtubule disturber. Our data suggest that microtubule stability promotes mitochondrial functional activity. In conclusion, a microtubule stabilizer can possibly recover mitochondrial functional activity in cells with unstable microtubules.

Land use and semen quality: A fertility center cohort study.

This study explored the association between built environment and semen parameters among men who sought fertility evaluation. We used a data of 5,886 men living in the Seoul capital area whose semen was tested at a single fertility center during 2016-2018. Distance to fresh water, the coast, major roadways, and neighborhood greenness measured by Normalized Difference Vegetation Index (NDVI) were evaluated. Outcome indicators were semen volume, sperm concentration, percentage of progressive motility, vitality, normal morphology, and total motile sperm count. Linear regression models were fitted to standardized values of six semen indicators. Majority of men were white-collar, clerical, and service workers. Linear associations between built environment features and semen quality indicators were not evident except for NDVI within 500 m and sperm vitality (ß = 0.05; 95% confidence interval (CI): 0.01, 0.09). The 2nd quartile of distance to fresh water was associated with lower progressive motility compared to the 1st quartile (ß = -0.10; 95% CI: -0.17, -0.03). Proportion of vitality was higher among men in the 2nd quartile of distance to roadways than those in the 1st quartile (0.08; 95% CI: 0.01, 0.15). Men in the 2nd quartile of NDVI had higher total motile sperm count (0.09; 95% CI: 0.01, 0.17). In the multi-exposure model, the positive association between NDVI and vitality remained (0.03; 95% CI: 0.00, 0.06). We observed potential evidence regarding the impact of built environment on male fertility, specifically a positive association between residential greenness and sperm vitality among men with a history of infertility.

The Effect of Additional Embryo Transfer on the Pregnancy Rate in Young Women Receiving in vitro Fertilization: A Natural Experiment Study.

PURPOSE: To assess the impact of additional embryo transfer (ET) on pregnancy in young women, we used a natural-experiment approach. PATIENTS AND METHODS: The design was based on the national policy of South Korea limiting the number of embryos transferred in vitro fertilization (IVF):≦2 embryos on day 2-4 or one on day 5-6 for patients aged <35, with one extra embryo allowed for patients aged ≥35. Using the data from 1909 ET cycles of 1287 women aged ≥34 and ≤35, we calculated adjusted risk ratios (RRs) for pregnancy. RESULTS: Half of cycles were undertaken by women aged 35, and additional ET was performed in 68.7% of them. Intrauterine pregnancy (45.2% vs 51.3%) and multiple gestation (30.5% vs 6.9%) were more common in women aged 35 than in those aged 34. The RR for intrauterine pregnancy was 1.34 (95% confidence interval: 1.12-1.59) when comparing double ET to single ET in frozen day 5-6 cycles. CONCLUSION: We observed no evidence of a higher probability of pregnancy with additional ET in fresh or frozen day 3-4 ET, or in fresh day 5-6 ET of women aged 35. Additional ET may not increase the successful pregnancy rate in the 35-year-old group, unless it is a frozen day 5-6 ET cycle.

The mitochondrial-derived peptide MOTS-c promotes homeostasis in aged human placenta-derived mesenchymal stem cells in vitro.

Mesenchymal stem cells (MSCs) are multipotent cells with critical roles in homeostasis and regeneration. MSCs undergo aging in response to various stresses, and this causes many diseases including degenerative disorders. Thus, regulation of aging factors is crucial for healthy aging. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) was recently reported to regulate metabolic homeostasis. Here, we investigated the restorative effects of MOTS-c on aged human placenta-derived MSCs (hPD-MSCs). MOTS-c promoted the morphology of old hPD-MSCs. MOTS-c significantly activated AMP-activated protein kinase, which is the main target pathway of MOTS-c, and inhibited its antagonistic effector mTORC1. MOTS-c considerably enhanced mitochondrial homeostasis by decreasing oxygen consumption and reactive oxygen species production. The mitochondrial state of MOTS-c-treated old hPD-MSCs was more similar to that of young hPD-MSCs than the mitochondrial state of non-treated old hPD-MSCs. MOTS-c also decreased lipid synthesis. In conclusion, we demonstrated that MOTS-c promotes homeostasis in aged hPD-MSCs.

Upregulation of Low-Density Lipoprotein Receptor of the Steroidogenesis Pathway in the Cumulus Cells Is Associated with the Maturation of Oocytes and Achievement of Pregnancy.

The maturation of the oocyte is influenced by cumulus cells (CCs) and associated with pregnancy rate, whereas the influencing factors have not been completely elucidated in the CCs. In this study, we identified new regulators of CCs for high-quality oocytes and successful pregnancies during assisted reproductive techniques. CCs were collected from cumulus-oocyte complexes (COCs) in young (≤33 years old) and old (≥40 years old) women undergoing intracytoplasmic sperm injection (ICSI) procedures. We screened for factors differentially expressed between young vs. old CCs and pregnancy vs. non-pregnancy using whole mRNA-seq-next-generation sequencing (NGS). We characterized the transcriptome of the CCs to identify factors critical for achieving pregnancy in IVF cycles. Women in the young and old pregnancy groups exhibited the up- and downregulation of multiple genes compared with the non-pregnancy groups, revealing the differential regulation of several specific genes involved in ovarian steroidogenesis in CCs. It was shown that the low-density lipoprotein (LDL) receptor to the steroidogenesis pathway was upregulated in CCs with higher maturity rates of oocytes in the pregnancy group. In conclusion, a higher pregnancy rate is related to the signaling pathway of steroidogenesis by the LDL receptor in infertile women undergoing IVF procedures.

Chromosomal abnormalities in spontaneous abortion after assisted reproductive treatment.

BACKGROUND: We evaluated cytogenetic results occurring with first trimester pregnancy loss, and assessed the type and frequency of chromosomal abnormalities after assisted reproductive treatment (ART) and compared them with a control group. We also compared the rate of chromosomal abnormalities according to infertility causes in ICSI group. METHODS: A retrospective cohort analysis was made of all patients who were referred to the Genetics Laboratory of Fertility Center of CHA Gangnam Medical Center from 2005 to 2009 because of clinical abortion with a subsequent dilation and evacuation (D&E) performed, and patients were grouped by type of conception as follows: conventional IVF (in vitro fertilization) (n = 114), ICSI (intracytoplasmic sperm injection) (n = 140), and control (natural conception or intrauterine insemination [IUI]) (n = 128). Statistical analysis was performed using SPSS software. RESULTS: A total 406 specimens were referred to laboratory, ten abortuses were excluded, and in 14 cases, we did not get any spontaneous metaphase, chromosomal constitutions of 382 specimens were successfully obtained with conventional cytogenetic methods. Overall, 52.62% of the miscarriages were found to be cytogenetically abnormal among all patients, the frequency was 48.4% in the control group, 54.3% of miscarriages after ICSI and 55.3% after conventional IVF (p = 0.503). The most prevalent abnormalities were autosomal trisomy, however, nine (11.69%) sex chromosome aneuploidy were noted in the ICSI group vs. four (6.45%) and two (3.23%) cases in the conventional IVF group and control group. We compared chromosomal abnormalities of miscarriages after ICSI according to infertility factor. 55.71% underwent ICSI due to male factors, 44.29% due to non-male factors. ICSI group having male factors showed significantly higher risk of chromosomal abnormalities than ICSI group having non-male factors (65.8% vs. 34.2%, p = 0.009, odds ratio = 1.529, 95% CI = 1.092-2.141). CONCLUSIONS: There is no increased risk of chromosomal abnormalities due to ART was found with the exception of a greater number of sex chromosomal abnormalities in the ICSI group with male factor infertility. Therefore, these alterations could be correlated with the underlying parental risk of abnormalities and not with the ICSI procedure itself.

Nighttime environmental noise and semen quality: A single fertility center cohort study.

With increased population and urban development, there are growing concerns regarding health impacts of environmental noise. We assessed the relationship between nighttime environmental noise and semen quality of men who visited for fertility evaluation. This is a retrospective cohort study of 1,972 male patient who had undertaken semen analysis between 2016-2018 at a single fertility center of Seoul, South Korea. We used environmental noise data of National Noise Information System (NNIS), Korea. Using semiannual nighttime noise measurement closest to the time of semen sampling, individual noise exposures at each patient's geocoded address were estimated with empirical Bayesian kriging method. We explored the association between environmental noise and semen quality indicators (volume, concentration, % of progressive motility, vitality, normal morphology, total motile sperm count, oligozoospermia, asthenozoospermia, and severe teratozoospermia) using multivariable regression and generalized additive models. Estimated exposure to nighttime environmental noise level in the study population was 58.3±2.2 Leq. Prevalence of oligozoospermia, asthenozoospermia, and severe teratozoospermia were 3.3%, 14.0%, and 10.1%. Highest quartile nighttime noise was associated with 3.5 times higher odds of oligozoospermia (95% CI: 1.18, 10.17) compared to lowest quartile. In men whose noise exposure is in 3rd quartile, odds ratio (OR) of severe teratozoospermia was 0.57 (95% CI: 0.33, 0.98). The OR for 4th quartile noise were toward null. In generalized additive model, the risk of oligozoospermia increases when the nighttime noise is 55 Leq dB or higher. Our study adds an evidence of potential impact of environmental noise on semen quality in men living in Seoul. Additional studies with more refined noise measurement will confirm the finding.