Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications.

Ovarian aging, a natural process in women and various other female mammals as they age, is characterized by a decline in ovarian function and fertility due to a reduction in oocyte reserve and quality. This phenomenon is believed to result from a combination of genetic, hormonal, and environmental factors. While these factors collectively contribute to the shaping of ovarian aging, the substantial impact and intricate interplay of chronic inflammation in this process have been somewhat overlooked in discussions. Chronic inflammation, a prolonged and sustained inflammatory response persisting over an extended period, can exert detrimental effects on tissues and organs. This review delves into the novel hallmark of aging-chronic inflammation-to further emphasize the primary characteristics of ovarian aging. It endeavors to explore not only the clinical symptoms but also the underlying mechanisms associated with this complex process. By shining a spotlight on chronic inflammation, the aim is to broaden our understanding of the multifaceted aspects of ovarian aging and its potential clinical implications.

Effect of artificial cycle with or without GnRH-a pretreatment on pregnancy and neonatal outcomes in women with PCOS after frozen embryo transfer: a propensity score matching study.

BACKGROUND: In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS. METHODS: A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors. RESULTS: After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight. CONCLUSION(S): In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of developing SGA babies.

Analysis of clinical outcomes of vitrified-warmed embryo transfer after IVF/ICSI at high altitude (3650 m) in Tibet.

RESEARCH QUESTION: What are the pregnancy outcomes of IVF vitrified-warmed embryo transfer (IVF-FET) carried out in a clinical setting located at an altitude of 3650 m in Tibet, China? DESIGN: A retrospective analysis of 238 infertility couples (n = 344 treatment cycles) who underwent FET treatment at the Xizang Fukang Hospital, Tibet. The overall clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate and ectopic pregnancy rate were statistically analysed. Women were categorized into two groups based on age: 35 years or younger (n = 265 cycles) and over 35 years (n = 79 cycles). The general characteristics and pregnancy outcomes were compared between the two groups. RESULTS: The clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, and ectopic pregnancy rate of the 344 FET cycles were 43.02%, 30.90%, 35.17%, 18.24% and 1.35%, respectively. The clinical pregnancy rate (46.04% versus 32.91%), implantation rate (33.92% versus 21.01%) and live birth rate (38.11% versus 25.32%) in the group aged 35 years or younger were significantly greater than those in the group aged over 35 years (P = 0.039, P = 0.004, P = 0.037). The miscarriage rate (17.21% versus 23.08%) and ectopic pregnancy rate (0.82% versus 3.85%) were not significantly different in the two groups. CONCLUSION: A live birth rate of 35.17% can be achieved with IVF-FET in high-altitude areas (3650 m above sea level). Maternal age is still an important determinant of clinical pregnancy rate, implantation rate, and live birth rate of infertile patients in high-altitude areas.

[Current progress in single sperm cryopreservation].

Sperm cryopreservation has been widely used in assisted reproduction, but conventional techniques are not suitable for the cryopreservation of small numbers of sperm. The application of the single sperm cryopreservation technique has significantly improved the clinical treatment of cryptozoospermia and non-obstructive azoospermia. Ever since Cohen et al first developed the method of single sperm cryopreservation in 1997, constant efforts have been made to develop the carriers for this technique. In this review, we mainly discuss the existing methods and clinical outcomes of single sperm cryopreservation.

Integration of hepatitis B virus into patients' sperm genome and its clinical risks.

BACKGROUND: Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. OBJECTIVES: To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. MATERIALS AND METHODS: Forty-eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group-1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group-2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty-eight healthy male donors were included as control. The standard semen parameter analysis, real-time polymerase chain reaction, quantitative real-time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. RESULTS: The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group-1 and Group-2 was not statistically significant. In Test Group-2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18 × 103/mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm-derived embryos through fertilization and retained their function in replication, transcription, and translation. CONCLUSION: Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer.

Young obese patients may benefit from GnRH-a long protocol contributing to higher implantation rate and live birth rate of fresh IVF-ET cycles.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy. Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019. Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups (P < 0.05). After adjusting for confounding factors, the logistic regression analysis showed that the GnRH-a long protocol group had higher probabilities of biochemical pregnancy, clinical pregnancy, and live birth than the GnRH-a protocol group. The Gn dose in the mGnRH-a group was higher than the other three groups. Whether single or twin, there were similar neonatal outcomes among the four groups including premature birth rate, Apgar score, newborn weight, and length. Conclusion: For young obese patients undergoing IVF-ET, the GnRH-a long protocol for COH gives better pregnancy outcomes.

Effects of sequential cleavage and blastocyst embryo transfer on pregnancy outcomes in patients with poor ovarian response.

The management of patients with poor ovarian response (POR) remains a major challenge for fertility specialists in in vitro fertilization-embryo transfer (IVF-ET). In this retrospective cohort study, we aimed to evaluate the clinical effect of sequential transfer on pregnancy outcomes in patients with POR. A total of 3579 POR patients who underwent the first frozen embryo transfer (FET) cycle were enrolled from January 2018 to April 2021. The patients were divided into three groups according to the embryo transfer (ET) strategy adopted: a study group that included POR patients in whom a cleavage-stage embryo (day 3) and a blastocyst (day 5/6) were transferred (sequential transfer group), and two control groups in whom two cleavage-stage embryos (D3-dET group) or two blastocysts (D5/6-dET group) were transferred. The study group was matched with the control groups at a ratio of 1:4 by propensity score matching (PSM). The main pregnancy outcomes measured were the live birth rate and multiple pregnancy rate. After PSM, the live birth rate in the sequential transfer group was significantly higher than that in the D3-dET group (44.2% vs. 34.3%, P = 0.019), and was similar to that in the D5/6-dET group (44.2% vs. 45.3%; P = 0.90). In addition, there was no increase in the risk of multiple pregnancy among POR patients undergoing sequential transfer compared with both D3-dET (26.7% vs. 25.6%, P = 0.85) and D5/6-dET (26.7% vs. 28.4%, P = 0.97) groups. These findings imply that sequential transfer is an effective option for POR patients and could be utilized after careful consideration.

An Individualized Recommendation for Controlled Ovary Stimulation Protocol in Women Who Received the GnRH Agonist Long-Acting Protocol or the GnRH Antagonist Protocol: A Retrospective Cohort Study.

Background: The GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified. Methods: This was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols. Results: After PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p<0.001). Stratified analysis showed that for those with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMI<24kg/m2,, the possibility of live births was similar between the two protocols [OR (95%CI), 1.06(0.60,1.89)], [OR (95%CI), 1.38(0.97,1.97)], [OR (95%CI), 0.99(0.72,1.37)]. Among the women with AMH levels ≤ 3 ng/ml and with were aged < 30years, regardless of BMI, the possibility of live birth was similar between the two protocols [OR (95%CI), 1.02(0.68,1.54)], [OR (95%CI), 1.43(0.68,2.98)]. Moreover, among women with AMH levels ≥ 6ng/ml, the possibility of live birth was similar between the two protocols [OR (95%CI),1.42(0.75,2.69)], [OR (95%CI),1.02(0.19,5.35)], [OR (95%CI), 1.68(0.81,3.51)], [OR (95%CI), 0.51(0.10,2.55)]. Conclusions: The suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients.

A cell clone strain from Mythimna separata (Lepidoptera: Noctuidae) highly susceptible to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and M. separata NPV (MsNPV).

In this study, we describe a cell line, Ms-10C, cloned from the line QAU-Ms-E-10 (simplified Ms-10), an embryonic line from Mythimna separata. The cloned cell line was significantly more sensitive to nucleopolyhedrovirus (NPV). Ms-10C cells were mainly spherical with a diameter of 14.42 ± 2.23 µm. DNA amplification fingerprinting (DAF) confirmed the profile of PCR-amplified bands of the cloned cell line was consistent with those of the parental cell line, Ms-10. The sequencing result of the mitochondrial cytochrome c oxidase I (mtCO I) fragment confirmed that the amplified 636-bps mtCOI fragment was 100% identical to that of M. separata. Its chromosomes exhibited the typical characters of lepidopteran cell lines. Its population doubling time was 42.2 h at 27°C. Ms-10C was more sensitive than Ms-10 to both Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and M. separata nucleopolyhedrovirus (MsNPV). At 4 d post infection, the infection rates of two viruses reached 94.2 and 92.3%, respectively. The availability of this cell clone strain will provide a useful tool for the basic research on nucleopolyhedrovirus and for potential application in expression of recombinant proteins with baculovirus expression vector system.

[Impact of sperm midpiece morphology on embryo development following intracytoplasmic morphologically selected sperm injection].

OBJECTIVE: To evaluate the impact of sperm midpiece morphology observed under high-power microscope on embryo development following intracytoplasmic morphologically selected sperm injection. METHODS: Morphologically normal sperms from 57 patients undergoing intracytoplasmic sperm injection (ICSI) for male-factor infertility were selected microscopically (magnification of ×200 or 400) and subjected to motile sperm organellar morphology examination (MSOME) at high magnification of ×6000. According to the morphology of sperm medpiece, the sperms were divided into 3 groups, namely group A with a/b of 1-1.2, group B with a/b≥1.5, and group C with irregular morphology. The sperms in the 3 groups were intracytoplasmically injected in oocytes and the outcomes of the embryos were compared. RESULTS: Groups A, B, and C showed significant differences in the rate of ET-D3 top quality embryo (79.7% vs 55.6 % vs 33.3%) and implantation rate (43.2% vs 11.1% vs 0%), but not in the fertilization rate (73.3% vs 80.4% vs 63.5%), blastocyst formation rate (23.2% vs 22.2% vs 9.09%), cryopreservation rate (29.2% vs 25.0 % vs 13.0%), or D3 top quality embryo rate (35.3% vs 37.8% vs 18.8%). CONCLUSIONS: In ICSI cycle, selecting morphologically normal sperms for intracytoplasic injection can increase the normal fertilization rate and top quality embryo rate on the transfer day and improve the implantation rate of the embryo.

[Intracytoplasmic injection of morphologically selected spermatozoa from patients with male factor infertility: clinical and embryo development outcomes].

OBJECTIVE: To test whether intracytoplasmic injection of morphologically selected spermatozoa (IMSI) from patients with male factor infertility can improve the clinical and embryo development outcomes of intracytoplasmic sperm injection-embryo transfer (ICSI-ET). METHODS: We performed IMSI for 82 couples diagnosed with obstructive azoospermia at high magnification (×6600) and traditional ICSI for another 91 couples using testicular sperms. We also performed IMSI for 44 couples with teratozoospermia at high magnification (×6600) and traditional ICSI for 71 patients using ejaculated sperms. The clinical and embryo development outcomes were compared between the cycles. RESULTS: For obstructive azoospermia, IMSI and ICSI showed no significant difference in the rates of cleavage (95.5% vs 96.7%), D3 top quality embryos (28.2% vs 29.2%), implantation (26.4% vs 32.3%), pregnancy (47.3% vs 50%), blastocyst formation (54.3% vs 54.6%), or abortion (14% vs 7.3%) (P>0.05), but a significantly higher normal fertilization rate was achieved in IMSI group (84.3% vs 77%, P<0.05). For teratozoospermia, the 2 techniques resulted in no significant differences in the rates of cleavage (96.2% vs 95.2%), D3 top quality embryo (27.6% vs 27.1%), implantation (28.2% vs 30.7%), pregnancy (43.7% vs 43.2%), or abortion (9.7% vs 10.5%) (P>0.05), but the normal fertilization rate (68% vs 75.5%) and the blastocyst formation rate (54.6% vs 67.9% ) were significantly higher in IMSI group (P<0.05). CONCLUSION: IMSI can improve the normal fertilization rates in couples with male factor infertility (including obstructive azoospermia and teratozoospermia) and increase blastocyst formation rate in cases of azoospermia.

[Study of growth pattern of cranialfacial complex based on skeletal age in children with normal occlusion in Shandong province].

PURPOSE: To establish the normal values of cephalometric items for children with normal occlusion in Shandong province, and study the growth tendency of them and analyze the characteristics in different skeletal stages and sexes. METHODS: Lateral cephalograph was taken in 172 children of Han nationality with normal occlusion in Shandong province. The pictures were processed by WinCeph7.0, and statistical analysis was carried out using SPSS18.0 software Package. The results between sexes and 4 skeletal stages were compared. RESULTS: Facial contour in males were larger than in females. With growth of children, counter-clockwise rotation happened in mandibular plane, and males rotated more than females. Maxillary anterior tooth tilted more forword in males than in females, while mandibular anterior tooth positioned more upright in males than in females, and the protrution of maxillary and mandibular anterior tooth in males decreased along with growth. The lower lip in males was thicker than in females. CONCLUSIONS: The normal values and standard deviations of measuring items in different gender and bone-age group were established. Supported by Natural Science Foundation of Shandong Province (ZR2009CM109) and Natural Science Foundation of Science and Technology Bureau of Shandong Province(2006GG3208004).