Effective protection: the embryonic development and clinical outcomes of emergency vitrification of 1246 oocytes and Day 0-Day 5 embryos in a natural disaster.

STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.

The reference value of anti-Müllerian hormone to diagnose polycystic ovary syndrome is inversely associated with BMI: a retrospective study.

BACKGROUND: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM). METHODS: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity. RESULTS: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m2, the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m2, the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m2, 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m2, 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m2, 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m2, 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001). CONCLUSIONS: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM.

Are ovarian responses and the number of transferable embryos different in females and partners of male balanced translocation carriers?

PURPOSE: To compare ovarian response and the number of transferable embryos between women with balanced autosomal translocations and women whose partners carry the translocation (control group). To investigate the predictive value of metaphase II (MII) oocyte number and biopsied embryo number for gaining at lowest one transferable embryo. DESIGN: We retrospectively analyzed 1942 preimplantation genetic testing for structural rearrangements (PGT-SR) cycles of 1505 balanced autosomal translocation couples over 8 years. All cycles were divided into two subgroups: Robertsonian and reciprocal translocations (ROBT and ReBT). Receiver operator characteristic (ROC) curves were plotted to ascertain a cutoff of MII oocytes and biopsied embryos as predictors of gaining at lowest one transferable embryo. RESULT: There were no statistical differences in baseline features or ovarian response indicators regarding the number of retrieved/MII oocytes, E2 level on the day of HCG, and ovarian sensitivity index (OSI) between women with balanced autosomal translocations and control group (P > 0.05). A decreased number of transferable embryos were found in women with balanced autosomal translocations regardless of the type of translocation. The cutoff values for gaining at lowest one transferable embryo are 12.5 MII oocytes and 4.5 biopsied embryos, respectively. CONCLUSION: Women with balanced autosomal translocations have a normal ovarian response, but fewer transferable embryos, meaning that higher gonadotropin (Gn) doses may be required to increase transferable embryos. When fewer than 12.5 MII oocytes or 4.5 blastocysts are obtained in a PGT-SR cycle, couples should be notified that the likelihood of gaining a transferable embryo is low.

The Combined Impact of Female and Male Body Mass Index on Cumulative Pregnancy Outcomes After the First Ovarian Stimulation.

Objectives: To evaluate the combined impact of male and female BMI on cumulative pregnancy outcomes after the first ovarian stimulation. Design: Retrospective cohort study. Setting: University-affiliated reproductive medicine center. Patients: A total of 15,972 couples undergoing their first ovarian stimulations from June 2009 to June 2016 were included. During the follow-up period between June 2009 and June 2018, 14,182 couples underwent a complete ART cycle involving fresh embryo transfer and subsequent frozen embryo transfers (FETs) after their first ovarian stimulations. Patients with a BMI <24 kg/m2 served as the reference group. Patients with a BMI ≥ 24 kg/m2 were considered to be overweight, and those with a BMI ≥28 kg/m2 were considered to be obese. Interventions: None. Primary Outcome Measure: The primary outcome was the cumulative live birth rate (CLBR), which defined as the delivery of at least one live birth in the fresh or in the subsequent FET cycles after the first ovarian stimulation. Results: In the analyses of females and males separately, compared with the reference group, overweight and obese females had a reduced CLBR (aOR 0.83, 95% CI 0.7.92 and aOR 0.76, 95% CI 0.64-0.90). Similarly, overweight males had a reduced CLBR (aOR 0.91, 95% CI 0.83-0.99) compared with that of the reference group. In the analyses of couples, those in which the male was in the reference or overweight group and the female was overweight or obese had a significantly lower CLBR than those in which both the male and female had a BMI <24 kg/m2. Conclusions: The CLBR is negatively impacted by increased BMI in the female and overweight status in the male, both individually and together.

Parental methylome reprogramming in human uniparental blastocysts reveals germline memory transition.

Uniparental embryos derived from only the mother (gynogenetic [GG]) or the father (androgenetic [AG]) are unique models for studying genomic imprinting and parental contributions to embryonic development. Human parthenogenetic embryos can be obtained following artificial activation of unfertilized oocytes, but the production of AG embryos by injection of two sperm into one denucleated oocyte leads to an extra centriole, resulting in multipolar spindles, abnormal cell division, and developmental defects. Here, we improved androgenote production by transferring the male pronucleus from one zygote into another haploid androgenote to prevent extra centrioles and successfully generated human diploid AG embryos capable of developing into blastocysts with an identifiable inner cell mass (ICM) and trophectoderm (TE). The GG embryos were also generated. The zygotic genome was successfully activated in both the AG and GG embryos. DNA methylome analysis showed that the GG blastocysts partially retain the oocyte transcription-dependent methylation pattern, whereas the AG blastocyst methylome showed more extensive demethylation. The methylation states of most known imprinted differentially methylated regions (DMRs) were recapitulated in the AG and GG blastocysts. Novel candidate imprinted DMRs were also identified. The production of uniparental human embryos followed by transcriptome and methylome analysis is valuable for identifying parental contributions and epigenome memory transitions during early human development.

[The level of the stress biomarker salivary alpha amylase is correlated with semen quality in infertile young men].

Objective: To investigate the relationship between the level of the stress biomarker salivary alpha amylase (SAA) and semen quality in infertile young men. METHODS: Totally, 313 infertile and 96 normal healthy men, aged 20－40 years old, were enrolled in this study. The SAA levels and semen parameters of the subjects were measured and compared between the two groups. RESULTS: Compared with the normal healthy controls, the young infertility patients showed a significantly higher SAA level (ï¼»141.04 ± 44.13ï¼½ vs ï¼»151.48 ± 38.42ï¼½ µmol/L, P < 0.05) and percentage of immotile sperm (IMS) (ï¼»39.98 ± 14.53ï¼½% vs ï¼»64.48 ± 26.32ï¼½%, P < 0.05), but lower sperm concentration (ï¼»44.23 ± 21.63ï¼½ vs ï¼»32.42 ± 23.07ï¼½ ×106/ml, P < 0.05) and percentage of progressively motile sperm (PMS) (ï¼»52.13 ± 15.42ï¼½% vs ï¼»27.91 ± 21.22ï¼½%, P < 0.05). Sperm concentration (ï¼»26.33 ± 31.83ï¼½ vs ï¼»35.28 ± 27.70ï¼½ ×106/ml, P < 0.05) and the percentage of PMS were remarkably lower in the infertile men with a high than in those with a low SAA level (ï¼»19.85 ± 21.55ï¼½% vs ï¼»31.70 ± 20.02ï¼½%, P < 0.05), while the percentage of IMS was higher in the former than in the latter group (ï¼»74.19 ± 26.84ï¼½% vs ï¼»59.92 ± 24.85ï¼½%, P < 0.05). The SAA level in the young infertility patients was correlated positively with the percentage of IMS (r = 0.170, P < 0.01), but negatively with sperm concentration (r = －0.227, P < 0.01) and the percentage of PMS (r = －0.468, P < 0.01). CONCLUSIONS: The stress biomarker salivary alpha amylase level in infertile young men is negatively correlated with semen quality, and therefore semen parameters can be improved by reducing the stress level.

Lower chromosomal abnormality frequencies in miscarried conceptuses from frozen blastocyst transfers in ART.

STUDY QUESTION: Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)? SUMMARY ANSWER: Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC. WHAT IS KNOWN ALREADY: Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge. STUDY DESIGN, SIZE, DURATION: This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA. MAIN RESULTS AND THE ROLE OF CHANCE: The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging.

Loss of follicles together with decreased oocyte quality and quantity contribute to age-associated ovarian senescence and infertility. Although underlying mechanisms for ovarian senescence are still unknown, mitochondrial dysfunctions have been reported. Here, we showed age-dependent decreases in ovarian Nicotinamide Adenine Dinucleotide (NAD+) levels in mice whereas supplementing aging mice with nicotinamide riboside (NR), an NAD+ precursor, increased ovarian NAD+ content. We found that increases in ovarian NAD+ levels in aging mice led to increased number of ovarian follicles and ovulatory potential as well as increased live birth rate. NR supplementation also reduced levels of reactive oxygen species and decreased spindle anomalies in aging oocytes, together with increased mitochondrial membrane potential (ΔΨm) and decreased mitochondrial clustering. In addition, NR supplementation improved ovarian mitochondrial energy metabolism. Our data suggested that supplementation with NAD+ precursors in vivo and in vitro could be potential therapeutic approaches for treating age-related ovarian infertility.

CdSe/ZnS quantum dots induced spermatogenesis dysfunction via autophagy activation.

Recent researches have demonstrated that many nanoparticles are harmful to spermatogenesis. However, the reported nanoparticles -elicited testicular pathologies have been mostly confined to hormone levels and sperm quality and quantity, the detail mechanism is still largely unknown and the strategies to reduce the toxicity of nanoparticles on testis are lacking. Here, we found that CdSe/ZnS quantum dots (QDs) exposure impair double-strand break (DSB) repair in spermatocyte, leading to the disruption of meiotic progression and thus cell apoptosis and decreased sperm production. Furthermore, we found that QDs exposure elevates the autophagy. Crucially, both in vitro and in vivo studies indicated that elevated autophagy could down-regulate the expression of the genes responsible for homologous recombination, which is the main pathway for DSB repair during meiosis, indicating that spermatogenesis impairment by CdSe/ZnS QDs is mediated by autophagy. Consequently, injection of autophagy inhibitor (3-MA) restore DSB repair in spermatocytes, resulting in prevention of spermatocyte apoptosis and recovery of spermatogenesis. Our studies strongly indicate that autophagy is key for eliciting the spermatogenesis dysfunction after nanoparticle exposure, and autophagy inhibition can be used as a potential clinical remedy for alleviating the male reproductive toxicity of nanoparticles.

Paternal age, body mass index, and semen volume are associated with chromosomal aberrations-related miscarriages in couples that underwent treatment by assisted reproductive technology.

We investigated the effects of paternal characteristics, including age, body mass index (BMI), and semen parameters on chromosomal aberration-related miscarriages in couples that underwent treatment with assisted reproductive technology (ART). Single nucleotide polymorphism (SNP) array analysis showed chromosomal aberrations in 60.2% (557/925) of miscarried fetuses, including trisomy in 73.1% (407/557) of cases. There were higher chromosomal aberration rates in fetuses for men aged 20-24 years and ≥30 years compared with controls. After adjusting for age and BMI of the female partners, and the BMI and semen parameters of the males, there was no statistically significant effect of paternal age ≥30 years on the risk of chromosomal aberrations-related miscarriages. However, the odds of chromosomal abnormality-related miscarriage were 148% higher for the youngest fathers (age: 20-24 years) than fathers aged 25-29 years [adjusted odds ratio (OR): 2.48, 95% confidence interval (CI): 1.03-5.96; P=0.042]. Furthermore, high male BMI (adjusted OR: 1.56, 95% CI: 1.14-2.14; P=0.005) and low semen volume (adjusted OR: 2.09, 95% CI: 1.06-4.11; P=0.034) were associated with increased risk of chromosomal aberration-related miscarriages. These findings demonstrate that very young paternal age, high BMI, and low semen volume are associated with increased risk of chromosomal aberration-related miscarriages in couples undergoing ART treatment.

Factors Associated with Ovarian Hyperstimulation Syndrome (OHSS) Severity in Women With Polycystic Ovary Syndrome Undergoing IVF/ICSI.

Introduction: Age, polycystic ovary syndrome (PCOS), low body mass index (BMI), high antral follicle count (AFC), increased anti-Muller hormone (AMH) levels, and elevated serum estradiol (E2) concentrations are risk factors for ovarian hyperstimulation syndrome (OHSS). However, data on the relationship between risk factors and OHSS severity in patients with PCOS are rare. Objective: This retrospective study examined the risk factors for OHSS and their effect on OHSS severity in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Method: The records of 2,699 women were reviewed and included in this study. These women were diagnosed with PCOS during their first IVF/ICSI cycle between January 2010 and December 2017. We analyzed the association between each of the interrogated risk factors (including female age, BMI, AFC, basal serum E2, and the number of oocytes retrieved) and OHSS. The effects of each risk factor on OHSS severity were further explored. Logistic regression was performed as part of the above analysis. Results: Of the 2,699 women with PCOS who underwent assisted reproductive technology (ART), 75.2% had a normal response to controlled ovarian hyperstimulation (COH), while 24.8% developed OHSS. All OHSS patients were younger and had lower BMIs and basal serum follicle-stimulating hormone (FSH) and E2 levels but higher AFCs than those in the normal group. AFC demonstrated a strong correlation with OHSS, with a cutoff value of 24 in patients with PCOS. A total of 19.5% of the patients had mild OHSS, while 80.5% had moderate OHSS. Compared with those in the moderate OHSS group, those in the mild OHSS group were older and had higher basal serum FSH levels and lower serum E2 and T levels. However, BMI and AFC were not different between the mild and moderate OHSS groups. Basal serum E2 showed a strong correlation with OHSS severity, with a cutoff value of 37.94 pg/ml. Conclusions: AFC is a strong marker of OHSS, and basal serum E2 is the best predictor of OHSS severity in women with PCOS undergoing IVF treatment.

A Slower Age-Related Decline in Treatment Outcomes After the First Ovarian Stimulation for in vitro Fertilization in Women With Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) patients have a better ovarian reserve and age-related improvement in endocrine disturbances than non-PCOS patients. The effects of age on in vitro fertilization (IVF) treatment outcomes associated with cumulative live birth rate (CLBR) remain unclear. Objectives: To study the effect of age on CLBR after the first ovarian stimulation in IVF in PCOS patients. Method: This retrospective cohort study included 3,502 PCOS patients and 18,596 patients with tubal factor infertility, who underwent their first IVF cycles and subsequent frozen embryo transfer (ET) attempts. The primary outcome was CLBR associated with a single stimulation cycle and secondary outcomes included the implantation rate, clinical pregnancy rate, live birth rate (LBR), large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm birth (PTB) rate of fresh ET cycles. Results: PCOS patients over 40 years had a higher implantation rate (27.8 vs. 15.7%, P < 0.05), clinical pregnancy rate (51.4 vs. 26.1%, P < 0.05), LBR (42.3 vs. 18.2%, P < 0.05), and CLBR (50.0 vs. 21.5%, P < 0.05) than non-PCOS patients over 40 years. These rates were comparable between PCOS patients aged 35 to 40 years and those aged over 40 years (P = 0.263, 0.385, and 0.112, respectively). The changes in the implantation rate, clinical pregnancy rate, and CLBR by age were slower for PCOS patients than for non-PCOS patients (all P < 0.05). Among PCOS patients less than 35 years, BMI was negatively associated with CLBR [aOR: 0.961 (0.939-0.985); P < 0.05]; however, among PCOS patients over 35 years, instead of BMI (P = 0.353), age [aOR: 0.891 (0.803-0.990); P < 0.05] and the number of oocytes retrieved [aOR: 1.093 (1.002-1.078); P < 0.05] were significantly associated with CLBR. No significant differences in LGA, LGA, or PTB were detected between PCOS and non-PCOS patients over 35 years (all P > 0.05). Conclusions: The declines in treatment outcomes with age are slower for PCOS patients than for non-PCOS patients. For patients over 40 years, PCOS patients have reproductive advantages over non-PCOS patients. In contrast to younger PCOS patients (<35 years), older PCOS patients (≥35 years) may benefit less from taking time to lose weight before IVF treatment, and the immediate initiation of assisted reproductive treatment is essential.

Impact of Female Obesity on Cumulative Live Birth Rates in the First Complete Ovarian Stimulation Cycle.

Background: Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. Objectives: To investigate whether the CLBR was compromised in obese women. Method: A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Results: Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m2 had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Conclusions: Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.

Shorter leukocyte telomere length is associated with risk of nonobstructive azoospermia.

OBJECTIVE: To determine the association between leukocyte telomere length and the risk of nonobstructive azoospermia (NOA). DESIGN: The mean leukocyte telomere length (LTL) among men with NOA, obstructive azoospermia (OA), and normospermic subjects was determined by quantitative polymerase chain reaction (PCR). We used logistic regression to investigate the association between LTL and the risk of NOA after adjustment for age and body mass index (BMI). Partial correlation analysis was also used to evaluate the relationship of clinical parameters with the mean LTL among men with OA and NOA. SETTING: Reproductive medicine center. PATIENTS(S): A total of 866 men, including 270 normospermic controls, 247 OA and 349 NOA patients. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Leukocyte telomere length. RESULT(S): The mean relative LTL of men with NOA was significantly shorter than that of those with OA and in normospermic controls (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.64-0.98 vs. OR 0.92, 95% CI 0.70-1.24 vs. OR 0.99, 95% CI 0.83-1.22), respectively). Subjects with shorter telomeres (lowest tertile) had a significantly higher risk of NOA than those with longer telomeres (highest tertile). Interestingly, we also found that a low relative LTL was associated with poor efficiency of spermatogenesis using the Johnsen score after testis biopsy and histopathology in azoospermic patients, after adjusting for patient age and BMI. CONCLUSION(S): This is the first report that short LTL is associated with NOA, shedding light on an important biological pathway involved in the etiology of this form of male factor infertility.

Publisher Correction: Chromatin analysis in human early development reveals epigenetic transition during ZGA.

In this Letter, the 'Open chromatin' label in Fig. 4a should have been centred above the first three columns, and the black horizontal line underneath the label should have been removed. In addition, there should have been a vertical black line between the last two sets of panels for consistency. Minor changes have also been made to Fig. 1 and to the legend of Fig. 3. These errrors have been corrected online, and see Supplementary Information to the accompanying Amendment for the original Fig. 4.

Chromatin analysis in human early development reveals epigenetic transition during ZGA.

Upon fertilization, drastic chromatin reorganization occurs during preimplantation development 1 . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) 2 . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing3-5. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.

Melatonin attenuates postovulatory oocyte dysfunction by regulating SIRT1 expression.

The quality of postovulatory metaphase II oocytes undergoes a time-dependent deterioration as a result of the aging process. Melatonin is considered to be an anti-aging agent. However, the underlying mechanisms of how melatonin improves the quality of postovulatory aged oocytes remain largely unclear. In this study, by using mouse model, we found that there were elevated reactive oxygen species levels and impaired mitochondrial function demonstrated by reduced mitochondrial membrane potential and increased mitochondrial aggregation in oocytes aged 24 h, accompanied by an increased number of meiotic errors, unregulated autophagy-related proteins and early apoptosis, which led to decreased oocyte quality and disrupted developmental competence. However, all of these events can be largely prevented by supplementing the oocyte culture medium with 10-3 M melatonin. Additionally, we found that the expression of sirtuin family members (SIRT1, 2 and 3) was dramatically reduced in aged oocytes. In addition, in vitro supplementation with melatonin significantly upregulated the expression of SIRT1 and antioxidant enzyme MnSOD, but this action was not observed for SIRT2 and SIRT3. Furthermore, the protective effect of melatonin on the delay of oocyte aging vanished when the SIRT1 inhibitor EX527 was used to simultaneously treat the oocytes with melatonin. Consistent with this finding, we found that the postovulatory oocyte aging process was markedly attenuated when the oocytes were treated with the SIRT1 activator SRT1720. In conclusion, our data strongly indicate that melatonin delays postovulatory mouse oocyte aging via a SIRT1-MnSOD-dependent pathway, which may provide a molecular mechanism support for the further application of melatonin in the assisted reproductive technology field.

In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients.

CONTEXT: Recently, two patients with primary ovarian insufficiency (POI) delivered healthy babies after in vitro activation (IVA) treatment followed by auto-transplantation of frozen-thawed ovarian tissues. OBJECTIVE: This study sought to report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in patients with POI, together with monitoring of follicle development and serum hormonal changes. DESIGN: This was a prospective observational cohort study. SETTING: We performed IVA treatment in 14 patients with POI with mean age of 29 years, mean duration since last menses of 3.8 years, and average basal FSH level of 94.5 mIU/mL. INTERVENTIONS: Prior to IVA treatment, all patients received routine hormonal treatments with no follicle development. We removed one ovary from patients with POI and treated them with Akt stimulators. We improved upon early procedures by grafting back fresh tissues using a simplified protocol. MAIN OUTCOME MEASURES: In six of the 14 patients (43%), a total of 15 follicle development waves were detected, and four patients had successful oocyte retrieval to yield six oocytes. For two patients showing no spontaneous follicle growth, human menopausal gonadotropin treatment induced follicle growth at 6-8 months after grafting. After vitro fertilization of oocyte retrieved, four early embryos were derived. Following embryo transfer, one patient became pregnant and delivered a healthy baby boy, with three other embryos under cryopreservation. CONCLUSION: IVA technology can effectively activate residual follicles in some patients with POI and allow them to conceive their own genetic offspring. IVA may also be useful for treating patients with ovarian dysfunction including aging women and cancer survivors.