Objective: To compare the survival outcomes between surveillance and adjuvant chemotherapy in patients with stage Ⅰ ovarian immature teratoma (IMT) underwent fertility-sparing surgery. Methods: Clinical and pathological records of patients with stage Ⅰ ovarian IMT between Jan. 2011 to Feb. 2023 were collected from Peking Union Medical College Hospital, except stage Ⅰa grade 1. The consultation of risks and benefits regarding adjuvant chemotherapy was conducted by gynecologic oncologists. A shared decision about surveillance or chemotherapy was made by physician and patients or their guardians. Patients who finally decided to undergo surveillance were included in the surveillance group (n=40), the others were included in the adjuvant chemotherapy group (n=63). Clinical characteristics, treatment and survival outcomes were analyzed and compared between two groups. Results: A total of 103 patients were included. The median age of initial diagnosis was 20 years old (range: 3-39 years old), and the median follow-up time was 31 months (range: 1-254 months). The age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, surgical method, and preoperative and postoperative alpha-fetoprotein levels in the surveillance group and the adjuvant chemotherapy group were similar (all P>0.05). The surgical approach and maximum tumor diameter between two groups were significantly different (all P<0.05). Forty patients of the surveillance group were identified, only one patient with stage Ⅰa grade 2 IMT who underwent cystectomy had malignant recurrence on the same ovary. Another 63 patients received adjuvant chemotherapy after surgery, five patients had malignant recurrence, and two of them died of disease progression after relapsed. There were no significant differences in disease-free survival (DFS;20 vs 36 months) and overall survival (OS; 23 vs 39 months) between the surveillance group and the adjuvant chemotherapy group (follow-up time censored at 72 months; DFS: P=0.325, OS: P=0.278). Conclusions: There are no differences in survival outcomes between patients with stage Ⅰ ovarian IMT underwent adjuvant chemotherapy or not. Active surveillance might be safe and preferable in stage Ⅰ IMT patients underwent complete resection of tumor.
Pregnancy ; Humans ; Female ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Prognosis ; Watchful Waiting ; Neoplasm Staging ; Ovarian Neoplasms/surgery* ; Chemotherapy, Adjuvant ; Teratoma/surgery* ; Retrospective Studies

OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fertilization in Vitro/methods* ; Ovarian Reserve ; Prospective Studies ; Premature Birth ; Embryo Transfer/methods* ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone/therapeutic use*

This study aims to investigate the efficacy and possible mechanism of Liuwei Dihuang Pills in the treatment of diminished ovarian reserve(DOR) by using proteomic techniques. Firstly, cyclophosphamide(60 mg·kg~(-1)) combined with busulfan(6 mg·kg~(-1)) was injected intraperitoneally to establish the mouse model of DOR. After drug injection, the mice were continuously observed and the success of modeling was evaluated by the disturbance of the estrous cycle. After successful modeling, the mice were administrated with the suspension of Liuwei Dihuang Pills by gavage for 28 days. At the end of the gavage, four female mice were selected and caged together with males at a ratio of 2∶1 for the determination of the pregnancy rate. Blood and ovary samples were collected from the remaining mice on the next day after the end of gavage. Hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM) were then employed to observe the morphological and ultrastructural changes in the ovaries. The serum levels of hormones and oxidation indicators were measured by enzyme-linked immunosorbent assay. Quantitative proteomics techniques were used to compare the ovarian protein expression before and after modeling and before and after the intervention with Liuwei Dihuang Pills. The results showed that Liuwei Dihuang Pills regulated the estrous cycle of DOR mice, elevated the serum levels of hormones and anti-oxidation indicators, promoted follicle development, protected the mitochondrial morphology of ovarian granulosa cells, and increased the litter size and survival of DOR mice. Furthermore, Liuwei Dihuang Pills negatively regulated the expression of 12 differentially expressed proteins associated with DOR, which were mainly involved in lipid catabolism, inflammatory response, immune regulation, and coenzyme biosynthesis. These differentially expressed proteins were significantly enriched in sphingolipid metabolism, arachidonic acid metabolism, ribosomes, ferroptosis, and cGMP-PKG signaling pathway. In summary, the occurrence of DOR and the treatment of DOR with Liuwei Dihuang Pills are associated with multiple biological pathways, mainly including oxidative stress response, inflammatory response, and immune regulation. "Mitochondria-oxidative stress-apoptosis" is the key to the treatment of DOR by Liuwei Dihuang Pills. YY1 and CYP4F3 may be the key upstream targets that trigger mitochondrial dysfunction and ROS accumulation, and the metabolism of arachidonic acid is the main signaling pathway of drug action.
Female ; Male ; Pregnancy ; Animals ; Mice ; Arachidonic Acid ; Ovarian Reserve ; Proteomics ; Ovary ; Lipid Metabolism

OBJECTIVE: Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms. METHODS: Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E₂), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction. RESULTS: Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E₂ and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment. CONCLUSION Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway.
Animals ; Female ; Follicle Stimulating Hormone ; Luteinizing Hormone ; Moxibustion ; Ovarian Reserve ; Phosphatidylinositol 3-Kinase/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pregnancy ; Proto-Oncogene Proteins c-akt/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; bcl-2-Associated X Protein/genetics*

OBJECTIVE: To explore the effect of electroacupuncture on endometrial receptivity and the pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) in the patients with diminished ovarian reserve (DOR). METHODS: Sixty-eight patients of DOR undertaken IVF-ET were randomized into an observation group (34 cases, 2 cases dropped off) and a control group (34 cases, 1 case dropped off). In the control group, endometrial preparation was performed according to the routine protocol. In the observation group, on the base of the treatment as the control group, acupuncture was applied to Geshu (BL 17), Shenshu (BL 23), Mingmen (GV 4), Shiqizhui (EX-B 8), Ciliao (BL 32), Zhongliao (BL 33), Tianshu (ST 25), Qihai (CV 6) and Guanyuan (CV 4), etc. Electric stimulation was given at Ciliao (BL 32)-Zhongliao(BL 33), Tianshu (ST 25)-Zigong (EX-CA 1), with disperse-dense wave, 2 Hz/15 Hz in frequency and tolerable current in intensity. Electroacupuncture was given once every two days, 3 times weekly, lasing 3 menstrual cycles till 1 day before embryo transfer. The endometrial thickness and morphology were observed on the day of human chorionic gonadotropin (HCG) of egg retrieval cycle, the day of endometrial transformation in frozen-thawed embryo transfer (FET) cycle and the day of embryo transfer in both groups successively; as well as HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate. RESULTS: In the observation group, the proportion of type A endometrium on the embryo transfer day was higher than those on HCG day of the egg retrieval cycle and the endometrial transformation day of FET cycle (P<0.05), and also higher than that of the control group (P<0.01). In the observation group, HCG positive rate, clinical pregnancy rate, embryo implantation rate and live birth rate were 75.0% (24/32), 71.9% (23/32), 47.4% (27/57) and 56.3% (18/32) respectively, and all higher than 36.4% (12/33), 30.3% (10/33), 18.0% (11/61) and 15.2% (5/33) in the control group separately (P<0.01). CONCLUSION Electroacupuncture improves the endometrial receptivity and IVF-ET pregnancy outcomes in the patients of diminished ovarian reserve.
Chorionic Gonadotropin ; Electroacupuncture ; Endometrium ; Female ; Fertilization in Vitro ; Humans ; Ovarian Diseases ; Ovarian Reserve ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate

OBJECTIVE: To investigate the effect of environmental estrogen bisphenol A (BPA) exposure on apoptosis of mouse ovarian preantral follicular granulosa cells and ovarian development and explore the underlying mechanism. METHODS: Mouse ovarian preantral follicular granulosa cells were isolated from female ICR mice at postnatal day (PND) 10 and cultured RESULTS: Compared with the control cells group, the isolated cells exposed to a low concentration of BPA (50 μmol/L) showed a significantly lowered apoptosis rate, increased mitochondrial membrane potential, and enhanced cellular proliferation ( CONCLUSIONS BPA can concentration-dependently regulate the function of ovarian preantral follicular granulosa cells in mice and potentially affects both the pregnant mice and the offspring female mice in light of early ovarian development.
Animals ; Apoptosis ; Benzhydryl Compounds ; Female ; Granulosa Cells ; Mice ; Mice, Inbred ICR ; Ovarian Follicle ; Phenols ; Pregnancy

OBJECTIVE: To observe the influence of regulating menstruation and promoting pregnancy acupuncture therapy on negative emotions in patients with premature ovarian insufficiency (POI). METHODS: A total of 60 patients with POI were randomly divided into an acupuncture group and a western medication group, 30 cases in each group. The acupuncture group was treated with regulating menstruation and promoting pregnancy acupuncture therapy at Baihui (GV 20), Shenting (GV 24), Guanyuan (CV 4), Sanyinjiao (SP 6), Shenshu (BL 23), Ciliao (BL 32), etc. once a day, 5 times a week for 3 months. The western medication group was treated by oral administration of climen. The drug was given 1 tablet a day for 21 days and was stopped for 1 week as a course. The treatment was required 3 consecutive courses. The self-rating anxiety scale (SAS) score, modified Kupperman index (KI) score, agitated and depressive symptom scores in KI and serum level of follicle stimulating hormone (FSH) before and after treatment were compared between the two groups. RESULTS: After treatment, the SAS scores, KI scores and serum levels of FSH in the two groups and the scores of agitated and depressive symptom in the acupuncture group were lower than those before treatment ( CONCLUSION Regulating menstruation and promoting pregnancy acupuncture therapy can effectively improve the negative emotions of patients with POI and reduce serum level of FSH .
Acupuncture Points ; Acupuncture Therapy ; Female ; Follicle Stimulating Hormone ; Humans ; Menstruation ; Pregnancy ; Primary Ovarian Insufficiency/therapy*

To study the clinical efficacy and safety of Bushen Huoxue Culuan Formula in treating infertility caused by diminished ovarian reserve(DOR) with kidney deficiency and blood stasis. A total of 100 DOR patients treated at Xiyuan Hospital, Acupuncture Hospital and Clinic of China Academy of Chinese Medical Sciences from 2017 to 2020 in line with the inclusion criteria were selected and randomly divided into experimental group and control group at the ratio of 1∶1. The experimental group was treated with Bushen Huoxue Culuan Formular, while the control group was treated with Climen and Clomiphene for 3 menstrual cycles. The ovulation rate, pregnancy rate, pregnancy success rate, serum hormone levels, and traditional Chinese medicine(TCM) symptom scores were observed in the 2 groups. The total effective rate was 92.00% in the experimental group and 72.00% in the control group, with a statistical difference between the two groups(P<0.01); the experimental group was superior to the control group in reducing FSH level, increasing AMH level, improving TCM symptoms, increasing pregnancy rate and pregnancy success rate, with a significant difference(P<0.05). There was no abnormal safety indicator and adverse reaction. Bushen Huoxue Culuan Formular is effective in treating infertility caused by DOR due to kidney deficiency and blood stasis, with a safety and reliability.
China ; Drugs, Chinese Herbal ; Female ; Humans ; Infertility, Female/drug therapy* ; Kidney ; Ovarian Reserve ; Pregnancy ; Reproducibility of Results ; Treatment Outcome

OBJECTIVE: To evaluate the clinical effect of acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy" on diminished ovarian reserve (DOR) and its influence on ovarian reserve function. METHODS: A total of 32 patients with DOR were treated by acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy". Acupoints group 1: Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Zigong (EX-CA 1), Dahe (KI 12), Zusanli (ST 36), Sanyinjiao (SP 6), Taichong (LR 3); acupoints group 2: Baihui (GV 20), Shenshu (BL 23), Ciliao (BL 32). Acupoints group 1 and group 2 were alternately used, and acupoints group 1 was used for the first time. The needles were stayed for 30 min each time, once every 1 or 2 days, 3 times a week, 36 times (3 months) as a course of treatment. The treatment could be continued until the patient was pregnant or the patient given up acupuncture, and the acupuncture was uninterrupted during menstruation. The changes of modified Kupperman scale score, serum sex hormones, anti-müllerian hormones (AMH), ovarian peak systolic velocity (PSV), resistive index (RI) and antral follicle count (AFC) were compared before and after treatment, and the clinical effect and pregnancy rate were observed. RESULTS: The total score of modified Kupperman scale after treatment was lower than that before treatment (<0.05); The total effective rate was 90.6% (29/32) and the pregnancy rate was 15.6% (5/32). After treatment, the levels of follicle stimulating hormone (FSH), FSH/ luteinizing hormone (LH) were lower than before treatment, ovarian PSV was higher than before treatment, RI was lower than before treatment, and AFC was more than before treatment (<0.05). CONCLUSION Acupuncture at "thirteen acupoints for regulating menstruation and promoting pregnancy" can effectively improve the ovarian reserve function of DOR patients.
Acupuncture Points ; Acupuncture Therapy ; Female ; Humans ; Infertility, Female ; therapy ; Menstruation ; Ovarian Reserve ; Pregnancy ; Prospective Studies

Primary ovarian pregnancy accounts for less than 1% of all cases of ectopic pregnancies. Its diagnosis is most commonly made intra-operatively and the approach in its management has been geared towards conservative measures such as oophorectomy and resection. Use of intrauterine device still remains the most established risk factor for the development of ovarian pregnancy. The diagnosis is established following the criteria first described by Spiegelberg in 1878. Several cases of ovarian gestation have been described in literature, although very few cases with live term fetus have been reported. Majority of the cases were diagnosed intra-operatively, and the management was tailored depending on the complexity of each of the different cases. This paper reports a case of primary ovarian pregnancy with a live term fetus, which was only diagnosed intra-operatively. Total hysterectomy with right salpingo-oophorectomy was performed due to difficulties encountered brought about by dense adhesions.
Pregnancy ; Female ; Pregnancy, Ectopic ; Pregnancy, Ovarian ;