Traditional Chinese medicine Dingkun pill to increase fertility in women with a thin endometrium—a prospective randomized study

ObjectiveThe aim of this study is to optimize the treatment methods of infertility, which is suggested to be mainly caused by thin endometrium, using a special form of traditional Chinese medicine, the Dingkun pill (DKP), to increase the beneficial endometrial effect of conventional hormone/progestogen therapy.MethodsA total of 307 patients visiting our specialized gynecological endocrinology department because of infertility, which we suggested to be caused by thin endometrium [endometrial thickness (EMT) < 7 mm], were randomly assigned to the experimental group and the control group. The experimental group was treated with estradiol + sequential dydrogesterone + DKP (every day); the control group received hormonal treatment without the Chinese medicine. All patients were monitored in terms of follicle diameter, EMT, and endometrial type every 2 days from the 8th to the 10th day of the menstrual cycle until ovulation day during three menstrual cycles. Serum progesterone levels on 7–8 days after ovulation were measured, and the cumulative pregnancy rate during three menstrual cycles between the two groups was compared.ResultsEMT on ovulation day in the experimental group was significantly higher than that in the control group (7.88 vs. 7.15 mm; p < 0.001). The proportion of type A and type B endometrium in total was significantly higher in the experimental group than that in the control group (83.2% vs. 77.7%; p < 0.05). Progesterone levels were significantly higher in the experimental group than those in the control group (10.874 vs. 10.074 ng/mL; p < 0.001). The cumulative pregnancy rate, the main outcome of the study, was significantly higher in the experimental group than that in the control group (29.2% vs. 15.7%; p < 0.05).ConclusionDKP added to conventional estrogen/progestogen therapy can significantly improve EMT and luteal function in patients attending due to infertility. Because this regimen increased the cumulative pregnancy rate in our study, we conclude that DKP can be used to increase the so-called “thin endometrium infertility”

Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation

BackgroundLeukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC).ObjectiveTo explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation.MethodCryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient’s MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice.ResultsFollicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse.ConclusionFor leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC

Ovarian tissue cryopreservation in the pediatric with rare diseases- experience from China’s first and the largest ovarian tissue cryobank

BackgroundThere is limited information about the efficacy of ovarian tissue cryopreservation (OTC) in children. In the present study, we report eight patients with rare diseases who underwent OTC in China’s first and largest ovarian tissue cryobank.ProcedureData from girls with rare diseases who underwent OTC between September 2020 and November 2022 were retrospectively analyzed. We also compared the number of cryopreserved cortex pieces, follicle number, and AMH in those with rare diseases and age-matched children with non-rare diseases who also underwent OTC in our cryobank.ResultsThe median age of the children was 5.88 ± 3.52 (range 2-13) years old. Unilateral oophorectomy was undertaken via laparoscopy in all of the children. The diseases in the 8 patients were: 4 mucopolysaccharidoses (MPS I two cases, IVA two cases), 1 Diamond-Blackfan anemia (DBA), 1 Fanconi anemia (FA), 1 hyperimmunoglobulin E syndrome (HIES), 1 Niemann-Pick disease. The number of cryopreserved cortex pieces was 17.13 ± 6.36, and the follicle count per 2 mm biopsy was 447.38 ± 524.35. No significant difference in age, the count of cryopreserved cortex pieces, follicle number per 2 mm biopsy, and AMH level was seen between the 20 children with non-rare diseases and those with rare diseases.ConclusionsThe reports help practitioners counsel girls with rare diseases about fertility preservation. The demand for OTC in pediatrics will likely grow as a standard of care

Abnormalities of early folliculogenesis and serum anti-Müllerian hormone in chinese patients with polycystic ovary syndrome

Abstract Purpose To investigate abnormalities of early folliculogenesis and Anti-Müllerian hormone (AMH) concentrations in polycystic ovary syndrome (PCOS) patients, and to analyze the association between AMH and early-stage follicle densities (FD). Methods A total of 175 patients underwent ovarian tissue cryopreservation in the first official cryobank in China, of which 16 patients aged 30–40 years old were diagnosed with endometrial cancer (all without initial chemo/radiotherapy), including 5 patients with concurrent PCOS and the other 11 patients without. We obtained standard cortical biopsies to measure FD using calcein staining. Blood samples were collected before cryopreservation to evaluate AMH concentrations. Results PCOS showed nearly three times the primordial and primary FD than NPCOS (P = 0.027), as well as more secondary preantral follicles (P = 0.002). A significantly higher proportion of secondary preantral follicles and a lower proportion of primordial and primary follicles were observed in PCOS (P = 0.01). Furthermore, the AMH concentration in PCOS was four times higher than that in NPCOS (P = 0.003), which is significantly correlated with primordial and primary follicle densities (r = 0.855, P < 0.001) and secondary preantral follicle densities (r = 0.732, P = 0.007). Conclusions We found significant disorders of early folliculogenesis in PCOS, which showed close correlation with increased AMH concentrations. To our knowledge, abnormalities of early-stage follicles have been shown for the first time in ovarian tissue of Chinese PCOS women. We suppose that the elevated AMH level is associated with abnormalities of early folliculogenesis within the complex PCOS pathogenesis, which may explain why AMH has the potential to be used as a biomarker for the diagnosis of PCOS. Our findings provide more implications for understanding the mechanism of PCOS, and new directions for further studies

Randomized study to prove the quality of human ovarian tissue cryopreservation by xenotransplantation into mice

Abstract Purpose To study the quality of our human ovarian tissue cryopreservation technique as performed in the first official "International Fertility Protection Centre" in China in patients with certain cancer types using a mouse model, and to find the best site for tissue transplantation in the mouse. Methods Thirty-six BALB/C female nude mice were randomly divided into 3 groups, group 1: control group; group 2: ovariectomized group; group 3: ovarian tissue transplantation group. Seventy-two pieces obtained from six ovarian tissue samples from each of three cancer patients were transplanted into the ovarian bursa cavity (OBC), the subcutaneous thigh (TS) and the subcutaneous neck (NS) and removed after 1.5 and 2.5 months, respectively. Follicular growth rate (FGR), total follicle surviving rate (TFSR), tissue recovery rate (TRR), antral follicles (AF), follicle stimulating hormone (FSH), estradiol (E2) and anti-Mullerian hormone (AMH) levels were measured. Results No significant differences in FGR, OBC, NS (p > 0.05); TFSR was 100% in OBC, NS and TS. No significant differences in TRR (p > 0.05); AF were found only in OBC; TFSR was 100% after transplantation; significantly higher FGR in the 2.5 months compared to the 1.5 months-group (p  < 0.05). AMH- and E2-level in group 1 and 3 were significantly higher than in group 2 (p < 0.05); in contrast, FSH was significantly lower. Conclusions After transplantation in the mice, the thawed ovarian tissue survived and follicles developed. The ovarian fossa site was the best site for transplantation. Our animal experiments can verify that our human ovarian tissue cryopreservation technique can preserve the quality of ovarian tissue. This is the essential precondition for successful re-transplantation into the patients after performing chemo/radiotherapy to protect ovarian function and fertility

Multi-omics analyses demonstrate the modulating role of gut microbiota on the associations of unbalanced dietary intake with gastrointestinal symptoms in children with autism spectrum disorder

ABSTRACTOur previous work revealed that unbalanced dietary intake was an important independent factor associated with constipation and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Growing evidence has shown the alterations in the gut microbiota and gut microbiota-derived metabolites in ASD. However, how the altered microbiota might affect the associations between unbalanced diets and GI symptoms in ASD remains unknown. We analyzed microbiome and metabolomics data in 90 ASD and 90 typically developing (TD) children based on 16S rRNA and untargeted metabolomics, together with dietary intake and GI symptoms assessment. We found that there existed 11 altered gut microbiota (FDR-corrected P-value <0.05) and 397 altered metabolites (P-value <0.05) in children with ASD compared with TD children. Among the 11 altered microbiota, the Turicibacter, Coprococcus 1, and Lachnospiraceae FCS020 group were positively correlated with constipation (FDR-corrected P-value <0.25). The Eggerthellaceae was positively correlated with total GI symptoms (FDR-corrected P-value <0.25). More importantly, three increased microbiota including Turicibacter, Coprococcus 1, and Eggerthellaceae positively modulated the associations of unbalanced dietary intake with constipation and total GI symptoms, and the decreased Clostridium sp. BR31 negatively modulated their associations in ASD children (P-value <0.05). Together, the altered microbiota strengthens the relationship between unbalanced dietary intake and GI symptoms. Among the altered metabolites, ten metabolites derived from microbiota (Turicibacter, Coprococcus 1, Eggerthellaceae, and Clostridium sp. BR31) were screened out, enriched in eight metabolic pathways, and were identified to correlate with constipation and total GI symptoms in ASD children (FDR-corrected P-value <0.25). These metabolomics findings further support the modulating role of gut microbiota on the associations of unbalanced dietary intake with GI symptoms. Collectively, our research provides insights into the relationship between diet, the gut microbiota, and GI symptoms in children with ASD