1.Advances in ovarian tissue cryopreservation and transplanta-tion for fertility preservation in prepubertal patients.
Jiaojiao CHENG ; Xiangyan RUAN ; Juan DU ; Fengyu JIN ; Muqing GU
Journal of Zhejiang University. Medical sciences 2025;():1-9
Ovarian tissue cryopreservation and transplantation is currently the only feasible method for preserving both fertility and ovarian endocrine function in prepubertal female patients. It is indicated for those requiring gonadotoxic therapies such as chemo-therapy, radiotherapy, or bone marrow transplantation for malignant diseases, as well as for non-malignant diseases, including immunologic, metabolic, and hematologic benign diseases requiring bone marrow transplantation, and other populations at high risk of premature ovarian insufficiency. The procedure involves laparoscopic retrieval of ovarian tissue, typically via unilateral oophorectomy in young patients, followed by slow-programmed cryopreservation. When the primary disease is cured and fertility or hormonal function restoration is desired, the tissue is thawed and transplanted, most commonly to an orthotopic site. For patients at high risk of ovarian malignancy involvement, pre-transplantation assessment of minimal residual disease in the ovarian cortex is performed using histo-pathology and molecular biology techniques. Globally, while ovarian tissue cryopreservation and transplantation has led to over 300 live births, the majority result from tissue cryopreserved after puberty. Successful restoration of puberty and subsequent live births following transplantation of tissue frozen before puberty, although demonstrated in reported cases, remain less common. Therefore, this review systematically summarizes recent advances in the indications, current application status, timing and strategies of ovarian tissue cryopreservation and transplantation, risk assessment of tumor cell reintroduction, and clinical outcomes in prepubertal patients. It also discusses the potential value and current challenges of combining this approach with invitro oocyte maturation techniques, ainming to provide practical references for clinical practice.
2.Diketopiperazines with anti-skin inflammation from marine-derived endophytic fungus Aspergillus sp. and configurational reassignment of aspertryptanthrins.
Jin YANG ; Xianmei XIONG ; Lizhi GONG ; Fengyu GAN ; Hanling SHI ; Bin ZHU ; Haizhen WU ; Xiujuan XIN ; Lingyi KONG ; Faliang AN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(8):980-989
Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans
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Aspergillus/chemistry*
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Diketopiperazines/isolation & purification*
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Anti-Inflammatory Agents/isolation & purification*
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Interleukin-1beta/genetics*
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Toll-Like Receptor 2/immunology*
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Propionibacterium acnes/drug effects*
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NF-kappa B/genetics*
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Molecular Structure
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Myeloid Differentiation Factor 88/immunology*
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Monocytes/immunology*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Cell Line
3.Impact of cryopreservation and thawing on human ovarian tissue
Yanglu LI ; Xiangyan RUAN ; Juan DU ; Jiaojiao CHENG ; Fengyu JIN ; Muqing GU ; Yanqiu LI ; O.Mueck ALFRED
Journal of Capital Medical University 2025;46(4):594-600
Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.
4.Progresses in the application of autologous platelet-rich concentrate in female fertility remodeling
Jiaojiao CHENG ; Xiangyan RUAN ; Juan DU ; Fengyu JIN ; Muqing GU ; Yanglu LI
Journal of Capital Medical University 2025;46(4):637-643
Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.
5.Impact of cryopreservation and thawing on human ovarian tissue
Yanglu LI ; Xiangyan RUAN ; Juan DU ; Jiaojiao CHENG ; Fengyu JIN ; Muqing GU ; Yanqiu LI ; O.Mueck ALFRED
Journal of Capital Medical University 2025;46(4):594-600
Objective To evaluate the impact of slow-freezing process on human ovarian tissue with the standard cryopreservation-thawing protocol of Fertility Protection Center of Beijing Obstetrics and Gynecology Hospital,Capital Medical University.Methods Ovarian tissues of 12 patients were divided into fresh ovarian tissue group(fresh group)and freezing-thawing ovarian tissue group(F-T group).The freezing-thawing protocol was the standard protocol in our center.The number and activity of follicle were examined with Hematoxylin-eosin(HE)staining and calcein-AM(calcein acetoxymethylester)staining,and the proliferation and apoptosis was evaluated with the immunohistochemical staining of Ki-67 and caspase-3.The expressions of apoptosis-related proteins such as caspase-3,bax and FasL between the two groups were compared with Western blotting.Results There were no statistically significant differences in follicle counting and follicle activity in ovarian tissues pre-and post-freezing-thawing(P>0.05),and the positive rate of Ki-67 in ovarian tissues after freezing-thawing was significantly lower than that in fresh ovarian tissues(P<0.05),and there was no statistically significant difference in the positive rate of caspase-3 between the two groups(P>0.05).The expression of caspase-3 protein in ovarian tissues after freezing-thawing was significantly higher than that in fresh ovarian tissues(P<0.05),while the expressions of other apoptosis-related proteins such as bax and FasL were not significantly different(P>0.05).Conclusion The standard cryopreservation-thawing regimen in our center can effectively maintain the follicle number,morphology,and activity in ovarian tissues.After freezing and thawing,the cell proliferation level is decreased.The expression of apoptosis-related proteins such as bax and FasL are not increased,and the expression of caspase-3 is relatively increased.These results suggest our freezing-thawing regimen is good for human ovarian tissue.
6.Progresses in the application of autologous platelet-rich concentrate in female fertility remodeling
Jiaojiao CHENG ; Xiangyan RUAN ; Juan DU ; Fengyu JIN ; Muqing GU ; Yanglu LI
Journal of Capital Medical University 2025;46(4):637-643
Female infertility is recognized as a global public health issue by the World Health Organization.Female fertility remodeling includes ovarian function reconstruction and uterus/endometrium reconstruction,etc.It is emerging as a hot technology since it is ready to prepare autologous platelet-rich concentrate and it is safer and more acceptable in autologous application.It plays an important role in regenerative medicine,and it is currently widely applied in maxillofacial and plastic surgery,dermatology and other clinical practices.This article mainly reviews the progresses of the application of autologous platelet-rich concentrate in female fertility remodeling.
7.Prevention and treatment of iatrogenic premature ovarian insufficiency:interpretation of the first Chinese guideline on ovarian tissue cryopreservation and transplantation
Ruan XIANGYAN ; Cheng JIAOJIAO ; Du JUAN ; Jin FENGYU ; Li YANGLU ; Gu MUQING ; O.Mueck ALFRED
Global Health Journal 2021;5(2):70-73
In recent years,with the rapid development of medical research,cancer diagnosis and treatment technology have significantly improved young cancer patient's survival rate.Anticancer therapy such as chemotherapy,radiother-apy,or hematopoietic stem cell transplantation can lead to premature ovarian insufficiency.The endocrine and reproductive function of the ovary is critical to women's physical and mental health.Ovarian tissue cryopreser-vation and transplantation can protect not only female fertility but also preserve ovarian endocrine function.This paper interprets the guidelines for ovarian tissue cryopreservation and transplantation issued by the Chinese Society of Gynecological Endocrinology affiliated to the International Society of Gynecological Endocrinology.The purpose of this guideline's interpretation is to promote more medical workers to understand the technology of ovarian tissue cryopreservation and transplantation,which can provide patients with more choices of fertility protection methods and improve their quality of life.
8.The progress and prospect of assessment measures of uterine cavity function for infertility patients
Zhang LUPING ; Ju RUI ; Ruan XIANGYAN ; Dai YINMEI ; Wang HUSHENG ; Jin FENGYU ; Jin JING ; Gu MUQING ; Cheng JIAOJIAO ; Yang YU ; Xu XIN ; Roemer THOMAS
Global Health Journal 2021;5(2):79-82
Objective:To explore the progress and prospect of evaluation methods for infertility patients.Methods:From September 2017 to December 2020,199 cases of infertility patients who have accepted mini-hysteroscopy examination in the Department of Gynecological Endocrinology,Beijing Obstetrics and Gynecology Hospital,Capital Medical University.The patients who had primary ovary insufficiency,tubal infertility were excluded;patients with hysteroscopy contradiction,such as acute or sub-acute vaginal tract inflammation,en-dometrium lesion or endometrium carcinoma,severe cardiovascular,liver or kidney insufficiency were excluded.40 patients were excluded and 15 patients lost follow up,144 patients were eventually included in the analysis.The patient's age,body mass index,infertility etiology,preoperative and postoperative stimulate ovulation cycle,pregnancy state and pregnancy time were recorded.The effect of mini-hysteroscopy on ovulation induction cycle was analyzed in pregnant patients.Results:The average age of 144 patients was 32.10±4.67 years old.96 (66.67%) patients were found to have intrauterine abnormalities,while 48 (33.33%) patients were found to have normal intrauterine cavity.48 cases of pregnancy,accounting for 33.33%;the median and interquartile ranges[M (Q1,Q3)]of ovulation induction cycles before and after surgery were respectively[3 (0,5)],[2 (1,3)],the difference was statistically significant(P < 0.05).Among the 48 pregnant patients,32 of them had no structural lesions in hysteroscopy,the ovula-tion induction cycle of these patients before and after hysteroscopy were respectively[5 (0,9)],[1 (0,3)],the difference was statistically significant (P < 0.05).Conclusion:Uterine cavity evaluation is important for the assessments of fertility.As an advanced diagnosis instrument,mini-hysteroscopy can not only timely detect the intrauterine abnormalities of patients,but also with great application value in shorten the ovulation cycle in infertility patients and increase the pregnancy rate.
9.A case report of cryopreserved ovarian tissue retransplantation in endometrial cancer
Xiangyan RUAN ; Jiaojiao CHENG ; Juan DU ; Yanglu LI ; Fengyu JIN ; Dan LU ; Rong ZHOU ; Yinmei DAI ; Qi ZHOU ; Matthias KORELL ; Husheng WANG ; Muqing GU ; Mueck Alfred O.
Chinese Journal of Reproduction and Contraception 2021;41(7):644-649
Objective:To preserve fertility and endocrine function of an endometrial carcinoma patient by ovarian tissue cryopreservation and transplantation.Methods:Part of the ovary was harvested and cryopreserved when surgery for a 33-year-old woman who was diagnosed with endometrial carcinoma. After the cancer reached remission, the patient underwent cryopreserved ovarian tissue transplantation. The endocrine hormone, follicle growth, and menopausal syndromes were detected.Results:One month after the surgery of transplantation, the modified Kupperman scores decreased from 12 to 2, and the menopausal syndrome disappeared. Two months after the operation of transplantation, the concentration of follicle-stimulating hormone (FSH) decreased to 21.78 IU/L, the level of estradiol increased from 13.76 ng/L to 65.55 ng/L, and follicle growth was observed by ultrasound. Four months after the surgery of transplantation, the level of FSH decreased to 6.26 IU/L, the level of estradiol increased to 112.22 ng/L. Nine months after the operation of transplantation, the level of estradiol was 118.14 ng/L, the level of progesterone increased to 8.96 μg/L, and two corpus luteum after ovulation were detected by ultrasound.Conclusion:Two months after the surgery of transplantation, the ovarian function has returned to normal, which demonstrated the success of transplantation of frozen-thawed ovarian tissue.
10.A case report of cryopreserved ovarian tissue retransplantation in endometrial cancer
Xiangyan RUAN ; Jiaojiao CHENG ; Juan DU ; Yanglu LI ; Fengyu JIN ; Dan LU ; Rong ZHOU ; Yinmei DAI ; Qi ZHOU ; Matthias KORELL ; Husheng WANG ; Muqing GU ; Mueck Alfred O.
Chinese Journal of Reproduction and Contraception 2021;41(7):644-649
Objective:To preserve fertility and endocrine function of an endometrial carcinoma patient by ovarian tissue cryopreservation and transplantation.Methods:Part of the ovary was harvested and cryopreserved when surgery for a 33-year-old woman who was diagnosed with endometrial carcinoma. After the cancer reached remission, the patient underwent cryopreserved ovarian tissue transplantation. The endocrine hormone, follicle growth, and menopausal syndromes were detected.Results:One month after the surgery of transplantation, the modified Kupperman scores decreased from 12 to 2, and the menopausal syndrome disappeared. Two months after the operation of transplantation, the concentration of follicle-stimulating hormone (FSH) decreased to 21.78 IU/L, the level of estradiol increased from 13.76 ng/L to 65.55 ng/L, and follicle growth was observed by ultrasound. Four months after the surgery of transplantation, the level of FSH decreased to 6.26 IU/L, the level of estradiol increased to 112.22 ng/L. Nine months after the operation of transplantation, the level of estradiol was 118.14 ng/L, the level of progesterone increased to 8.96 μg/L, and two corpus luteum after ovulation were detected by ultrasound.Conclusion:Two months after the surgery of transplantation, the ovarian function has returned to normal, which demonstrated the success of transplantation of frozen-thawed ovarian tissue.

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