Anti-Müllerian hormone (AMH) is now accepted as an important clinical marker of ovarian reserve and is increasingly measured as an initial evaluation at infertility clinics. The aim of this study was to establish reference values for the revised second generation (Gen II) assay using population-based data. In this population-based cohort study, AMH data from unselected infertile women aged 25–45 years from June 2013 to June 2014 (n = 15,801) were collected. The AMH values were measured using the revised Gen II assay. We established and validated 5 AMH-age regression models. Based on the optimal AMH-age model, reference values and centile charts were obtained. The quadratic model (log AMH = 0.410 × age − 0.008 × age²− 3.791) was the most appropriate for describing the age-dependent decrease in AMH measured using the revised Gen II assay. This is the largest population-based study to establish age-specific reference values of AMH using the revised Gen II assay. These reference values may provide more specific information regarding the ovarian reserve estimation of infertile women.
Biomarkers ; Cohort Studies ; Female ; Humans ; Infertility ; Ovarian Reserve ; Reference Values*

To summarize LIU Zhi-shun's clinical experience in treatment of infertility with decreasing ovarian reserve (DOR) with electroacupuncture. LIU Zhi-shun believes that the location of infertility with DOR is the uterus, mainly involving the kidney, thoroughfare and conception vessels. He advocates to select acupoints by combining "disease-symptom-position" with prescription, and selects acupoint prescription of Bushen Tiaochong Zhuyun included Guanyuan (CV 4), Zigong (EX-CA 1), Tianshu (ST 25), Sanyinjiao (SP 6), Ciliao (BL 32) and Zhongliao (BL 33) for electroacupuncture treatment. The key points of operation are accurate positioning and deep acupuncture, focusing on regulating mind and getting qi, adopting electroacupuncture treatment and low frequency stimulation and treating slowly for long-term disease.
Acupuncture Points ; Acupuncture Therapy ; Electroacupuncture ; Female ; Humans ; Infertility ; Ovarian Reserve

The present study investigated the effect of Modified Dihuang Decoction in improving ovarian reserve in mice through the Bcl-2-related mitochondrial apoptosis pathway. Forty-eight adult female BALB/c mice were randomly divided into the following six groups with eight mice in each group: a blank group, a model group, a femoston group(three cycles of treatment with 0.13 mg·kg~(-1) estradiol tablets for 2 days and 1.43 mg·kg~(-1) estradiol and dydrogesterone tablets for 3 days), and high(64.74 g·kg~(-1))-, medium(43.16 g·kg~(-1))-, and low-dose(21.58 g·kg~(-1)) Modified Dihuang Decoction groups. Mice in other groups except the blank group received a single intraperitoneal injection of 12 mg·kg~(-1) cyclophosphamide and 1.2 mg·kg~(-1) busulfan to induce a model of diminished ovarian reserve(DOR), while those in the blank group received an equal volume of normal saline. Mice were treated with corresponding drugs for 15 d from the 36 th day, once per day, and the mice in the blank group and the model group were treated with an equal volume of normal saline. The general condition and oestrous cycle were observed. The serum hormone levels were detected with the enzyme-linked immunosorbent assay(ELISA). The morphological changes of ovaries were observed by HE staining. Western blot was used to detect the protein expression of cysteinyl aspartate specific proteinase-9(caspase-9), cleaved caspase-3, Bcl-2 associated X protein(Bax), Bcl-2, superoxide dismutase-2(SOD-2), and glutathione peroxidase-1(GPx-1). The mRNA expression of Bax and Bcl-2 was detected by real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR). The results showed that compared with the blank group, the model group showed body weight loss, disordered oestrous cycle, elevated serum levels of follicle-stimulating hormone(FSH) and luteinizing hormone(LH), reduced serum levels of estradiol(E_2), anti-mullerian hormone(AMH), and inhibin B(INHB), the declining number of ovarian follicles and granulosa layers, increased number of atretic follicles, up-regulated protein expression of caspase-9, cleaved caspase-3, and Bax and Bax mRNA expression in ovaries, and down-regulated protein expression of Bcl-2, SOD-2 and GPx-1, and Bcl-2 mRNA expression. Compared with the model group, the Modified Dihuang Decoction groups displayed restored body weight and oestrous cycle, decreased serum levels of FSH and LH, elevated serum levels of E_2, AMH, and INHB, increased number of ovarian follicles, thickened granulosa layers, and declining number of atretic follicles. Additionally, the protein expression of caspase-9, cleaved caspase-3, and Bax, and Bax mRNA expression was down-regulated, and the protein expression of Bcl-2, SOD-2, and GPx-1, and Bcl-2 mRNA expression was up-regulated. The results suggest that Modified Dihuang Decoction can regulate endocrine hormone, promote follicle growth and improve ovarian reserve by enhancing ovarian anti-oxidant capacity, inhibiting the Bcl-2-related mitochondrial apoptosis pathway, and further inhibiting cell apoptosis.
Animals ; Apoptosis ; Female ; Mice ; Mice, Inbred BALB C ; Ovarian Follicle ; Ovarian Reserve ; Ovary

The ovarian reserve is necessary for female fertility and endocrine health. Commonly used cancer therapies diminish the ovarian reserve, thus, resulting in primary ovarian insufficiency, which clinically presents as infertility and endocrine dysfunction. Prepubertal children who have undergone cancer therapies often experience delayed puberty or cannot initiate puberty and require endocrine support to maintain a normal life. Thus, developing an effective intervention to prevent loss of the ovarian reserve is an unmet need for these cancer patients. The selection of adjuvant therapies to protect the ovarian reserve against cancer therapies underlies the mechanism of loss of primordial follicles (PFs). Several theories have been proposed to explain the loss of PFs. The “burn out” theory postulates that chemotherapeutic agents activate dormant PFs through an activation pathway. Another theory posits that chemotherapeutic agents destroy PFs through an “apoptotic pathway” due to high sensitivity to DNA damage. However, the mechanisms causing loss of the ovarian reserve remains largely speculative. Here, we review current literature in this area and consider the mechanisms of how gonadotoxic therapies deplete PFs in the ovarian reserve.
Adolescent ; Child ; DNA Damage ; Female ; Fertility ; Fertility Preservation ; Humans ; Infertility ; Ovarian Follicle ; Ovarian Reserve ; Primary Ovarian Insufficiency ; Puberty ; Puberty, Delayed

Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function.
Cross-Sectional Studies ; Female* ; Gonadotropin-Releasing Hormone* ; Humans ; Ovarian Reserve ; Puberty, Precocious* ; Reference Values

Endometriosis is a chronic inflammatory disease that affects 10% to 15% of all women of reproductive age. Several studies show an association between endometriosis and infertility; however, clear causality remains unproven. The association between endometriosis and infertility is attributable to distorted pelvic anatomy secondary to adhesions, altered endocrine and ovarian function, impaired uterine implantation, and poor quality of oocytes/embryos. Medical treatment shows limited efficacy, without any evidence to support its role in improving fertility. Surgical treatment can improve ongoing pregnancy rates in minimal-to-mild endometriosis, although this approach may cause inevitable ovarian injury in women with ovarian endometrioma. Tailored treatment should be used in women with infertility and endometriosis. Age, ovarian reserve, a history of ovarian surgery, and bilateral endometriomas are important factors that should be carefully considered in these cases.
Endometriosis ; Female ; Fertility ; Humans ; Infertility ; Ovarian Reserve ; Pregnancy Rate ; Reproductive Techniques, Assisted

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

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

Diminished ovarian reserve (DOR), generally defined as a decreased number or quality of oocytes, has a significant impact on quality of life and fertility in women. In recent years, the incidence of DOR has been increasing and the ages of patients are younger. The search for an effective DOR treatment has emerged as one of the preeminent research topics in reproductive health. An effective DOR therapy would improve ovarian function, fertility, and quality of life in patients. In this review we evaluated DOR treatment progress both in Western medicine and Chinese medicine, and elucidated the characteristics of each treatment.
Female ; Humans ; Medicine, Chinese Traditional ; Ovarian Reserve ; Quality of Life ; Oocytes ; Treatment Outcome ; Infertility, Female/therapy*

OBJECTIVE: To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR). METHODS: A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment. RESULTS: Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E₂ elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups. CONCLUSIONS BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.
Anti-Mullerian Hormone/pharmacology* ; Drugs, Chinese Herbal ; Female ; Follicle Stimulating Hormone ; Humans ; Luteinizing Hormone ; Ovarian Reserve