| BackgroundDiminished ovarian reserve(DOR)refers to the decreased production of mature ova in ovarium and decreased quality of oocyte,leading to deficiency of the female sex hormone and decreased fertility.Clinical manifestations of diminished ovarian reserve patients include oligomenorrhea,hypomenorrhea,amenorrhea and infertility.Approximately 10%of women seeking fertility treatment have diminished ovarian reserve.DOR is a complex clinical phenomenon that is influenced by age,genetics and environmental variables.There is noted upward trend in the incidence of diminished ovarian reserve.Diminished ovarian reserve may also have adverse implications for a woman's wellbeing beyond her reproductive concerns.Changes in ovarian hormones,concomitant with DOR,can cause accelerated bone turnover,low bone mineral density,sexual dissatisfaction and disturbed sleep.Presently,aging is the primary cause of diminished ovarian reserve,while diminished ovarian reserve can also result from the consequence of the ovary having been damaged or destroyed from disease processes.One of the most common diseases is endometriosis.Other types of benign ovarian tumors and even borderline malignant tumors of the ovary can also destroy ovarian tissue.Surgical removal of ovarian disease frequently results in the removal of some normal ovarian tissue,as well.It is also not uncommon for women to lose an ovary from surgery for a fallopian tube problem and/or a surgery for a benign ovarian problem.Ovarian tissue may also be destroyed by an autoimmune process in which antibodies attack the follicles that contain oocytes within the ovary.In addition to the above described conditions,there can be no apparent cause for some diminished ovarian reserve patients.Once DOR is identified,treatments are designed to hasten the time to conception,or to cryo-preserve(freeze)eggs or embryos for a patient's future use.Main treatments for diminished ovarian reserve can be listed as follows:Controlled ovarian hyperstimulation with intrauterine insemination cycles(COH/IUI):stimulatory hormones can be injected in order to maximize the number of mature eggs each month.With pelvic ultrasound and lab work monitoring,a properly timed insemination can be performed.The sperm used for insemination has been prepared to optimize motility and is delivered directly into the uterus as close to the ovulating egg(s)as possible.In vitro fertilization(IVF)cycles:IVF attempts to simultaneously stimulate multiple eggs to mature at one time.The process involves injecting stimulation hormones and monitoring the ovaries' response with pelvic ultrasound and lab work.When the proper parameters are reached,another hormone is injected for final maturation of the eggs.The eggs are then retrieved surgically through the vagina,fertilized with sperm,and cultured in the embryology laboratory for several days before transferring into the woman's uterus where implantation hopefully results.Ovarian stimulation protocols are the prescribed mix of hormones tailored to each woman during fertility treatments.These protocols need to be refined for women with advanced reproductive aging and/or diminished ovarian reserve to maximize chances of success with fertility treatments.Patients with DOR who are undergoing IVF are typically placed on higher doses of ovarian stimulation regimens in an effort to maximize the number of eggs harvested.However,once the ovary has failed to respond to stimulation,or later fails endocrinologically,donor eggs are recommended to restore a woman's reproductive potential.By using eggs donated by young women,who are typically in their 20s,women with DOR may conceive and successfully deliver a baby,even long after menopause.The prognosis for women with DOR is guarded once the diagnosis is made.Even in the earliest stages DOR reduces pregnancy success and contributes to an increase in miscarriages.The older the patient,the more compromised the clinical picture typically becomes.Hormone replacement therapy is used for patients with no fertility requirements.Benefits of HRT include:reduction in vasomotor symptoms,improvement in quality of life,improvement in mood changes,improvement of urogenital symptoms,reduction in osteoporosis risk,reduction in cardiovascular disease,lower risk of colorectal cancer and so on.To be more specific,HRT can also improve sleep,muscle aches and pains,HRT can improve mood and also depressive symptoms.HRT should be considered to alleviate low mood.Cognitive behavioral therapy may be beneficial too.Various studies have shown that HRT significantly improves vaginal dryness and sexual function.HRT is effective in improving the symptoms related to vaginal atrophy.HRT can also relieve the symptoms of urinary frequency,as it has a proliferative effect on the bladder and urethral epithelium.Topical oestrogen is very effective in improving urinary symptoms in menopausal women.Vaginal symptoms are improved,vaginal atrophy and there is improved epithelial maturation with topical oestrogen preparations compared to placebo or non-hormonal gels.Oestrogens are the most effective way of increasing bone mineral density(BMD)and also preventing osteoporotic fractures in women.The relation between HRT and cardiovascular disease is controversial but the timing and duration of HRT,as well as pre-existing cardiovascular disease,are likely to affect outcomes.Colorectal cancer risk was reduced in women taking combined conjugated equine oestrogens and medroxyprogesterone acetate.However,risks can be associated with hormone replacement therapy.The principalrisks of HRT are thromboembolic disease(venous thromboembolism(VTE)and pulmonary embolism),stroke,breast and endometrial cancer,and gallbladder disease.Large studies in the past cast concerns and controversy over the use of HRT.Firstly,the type,dose and delivery system of both oestrogen and progestogen influence the risk of thromboembolic disease.The risk of VTE is increased two to three times with oral HRT.These risks increase with age and with other risk factors,such as obesity,previous thromboembolic disease,smoking and immobility.Transdermal HRT should be given for those women with an increased risk of VTE.Secondly,HRT can increase the risk of ischaemic stroke.It is associated with a small increased risk in women taking oral oestrogen-only or combined HRT.Thirdly,combined HRT increases the risk of breast cancer,endometrial cancer,Ovarian cancer.Combined HRT also increases breast density and the risk of having an abnormal mammogram.The dose,regimen and duration of HRT need to be individualised.There is no maximum duration of time for women to take HRT;for the women who continue to have symptoms,their benefits from HRT usually outweigh any risks.Side-effects of HRT include:Oestrogen:breast tenderness,leg cramps,bloating,nausea,headaches.Progestogen:premenstrual syndrome-like symptoms,breast tenderness,backache,depression,pelvic pain.Bleeding:monthly sequential preparations should produce regular,predictable and acceptable bleeds starting towards the end,or soon after,the progestogen phase.Breakthrough bleeding is common in the first 3-6 months of continuous combined and long-cycle HRT regimens.For patients have fertility requirements,outcomes of ovulation induction and assisted reproductive technology is still not satisfactory There are some reports that immunosuppressors like glucocorticoid can recover ovulation and promote pregnancy,reported,but long-term adverse reactions is severe and the effect is not exact.DOR is not identified in traditional Chinese medicine(TCM),but is classified as a symptom of delayed menorrhea,oligomenorrhea,amenorrhea,irregular menstrual cycle and infertility.In China,patients with DOR often choose alternative treatments,such as herbs and acupuncture.The use of acupuncture for the treatment of female infertility has a long history.It was first proposed for the treatment of gynecological diseases based on the syndrome differentiation of traditional Chinese medicine by three gynecological monographs in a book named Synopsis of Golden Chamber compiled by Zhang Zhongjing at the end of the Eastern Han Dynasty.Acupuncture has been used to relieve pain during egg retrieval,promote ovulation,improve endometrium,and enhance pregnancy rate by assisted reproductive technology.Acupuncture is gaining its popularity for effectiveness and safety.Clinical trials showed that acupuncture can improve the serum hormone levels,menstrual status and success rate of IVF.Also,experimental studies have proved that some acupoints can enhance ovarian function and delay its decline,increase the level of E2 and improve the hypothalamic pituitary gonadal axis function.There are few literatures on the treatment of ovarian reserve by acupuncture and moxibustion,and most of them are the combination of acupuncture and medicine.At present,etiology and pathogenesis,syndrome differentiation and treatment has not yet formed a complete theoretical system in the the light of of TCM.We relatively lack of relevant documents and reports of this disease,and lack of extensive and in-depth and high quality of clinical curative effect reseach and acupuncture mechanism study.Professor Fang Yigong has engaged in research of treating DOR with acupuncture for many years,using "tiao jing cu yun acupuncture therapy".Professor Fang puts emphasis on balance of chong and ren meridian,kidney essence and emotional influence.He highlights the unique characteristics and prominent effect of acupuncture.For DOR may end up with premature ovarian failure,early intervention by acupuncture meet the idea of TCM disease prevention.Objective(1)To sum up the treatment experience of Professor Fang and explore the effectiveness of acupuncture for treating DOR.(2)This preliminary study may benefit future multi-centred,large sample clinical research.MethodWe screened DOR patients who visited China academy of traditional Chinese medicine acupuncture hospital during January 2016-April 2017.46 patients who met the DOR diagnostic criteria and signed innformed consent were divided into 2 groups—acupuncture group and waiting group according to randomization,23 cases in each group.With measurement of serum hormone level(follicle stimulating hormone,luteinizing hormone,follicle stimulating hormone/luteinizing hormone,estradiol),Anti Mueller hormone,Antral follicle,menstrual symptom score and Self rating Anxiety Scale for curative effect,respectively,Before treatment/waiting,and after treatment/waiting,we assessed the efficacy.40 patients finished this research.Results(1)46patients participated,6 dropouts,40 cases completed treatment,20 cases in acupuncture group and 20 cases in waiting group.There was no statistically significant difference in age,course,severity between two groups.The total loss rate was 13.4%.No serious adverse events occurred during the trial(2)Before and after treatment/waiting between groups,the FSH value of the acupuncture group was decreased and the difference was statistically significant(P=0.00<0.05).There was no significant change in the waiting group(P=0.17>0.05).P-value of the two groups after treatment/waiting showed that acupuncture group was more obvious,the difference between the two groups was statistically significant(P=0.002<0.05).(3)Before and after treatment/waiting between groups,the normal rate of FSH/LH of the acupuncture group was increased and normal rate of FSH/LH of the waiting group was decreased.The P-value between the two groups was statistically significant(P=0.047<0.05).(4)Before and after treatment/waiting between groups,the E2 value of the acupuncture group was increased and the difference was statistically significant(P=0.008<0.05).There was no significant change in the waiting group(P=0.91>0.05).P-value of acupuncture group was more obvious and the difference between the two groups was statistically significant(P=0.006<0.05).(5)Before and after treatment/waiting between groups,the AMH value of the acupuncture group was changed but the difference was no statistically significant(P=0.86>0.05).There was no significant change in the waiting group(P=0.65>0.05).P-value of the two groups after treatment/waiting was no statistically significant(P=0.89>0.05).(6)Before and after treatment/waiting between groups,the AFC of the acupuncture group was increased and the difference was statistically significant(P=0.001<0.05).There was no significant change in the waiting group(P=0.44>0.05).P-value of the two groups after treatment/waiting showed that acupuncture group was more obvious,the difference between the two groups was statistically significant(P=0.008<0.05).(7)Before and after treatment/waiting between groups,the menstrual symptom score of the acupuncture group decreased and the difference was statistically significant(P=0.005<0.05).There was no significant change in the waiting group(P=1.00>0.05).P-value of the two groups after treatment/waiting showed that acupuncture group was more obvious,the difference between the two groups was statistically significant(P=0.011<0.05).(8)Before and after treatment/waiting between groups,the SAS scale of the acupuncture group decreased and the difference was statistically significant(P=0.01<0.05).There was no significant change in the waiting group(P=0.31>0.05).P-value of the two groups after treatment/waiting showed that acupuncture group was more obvious,the difference Etween the two groups was statistically significant(P=0.006<0.05).(9)Safety analysis:2 cases appeared needle sticking;6 cases appeared subcutaneous ecchymosis during treatment.All patients had no serious adverse reactions.Conclusion"Tiao jing cu yun acupuncture therapy"can improve serum hormone level of patients,increase antral follicle count,improve menstrual and anxiety status.After acupuncture treatment,the number of the patients who were recovered markedly improved,effective rate was significantly higher than the waiting group and there was no significant adverse reaction.To conclude,this trial proved "Tiao jing cu yun acupuncture therapy" to be a safe and effective for treating diminished ovarian reserve. |
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