| BackgroundPremature ovarian insufficiency(POI)is a clinical syndrome defined by loss of ovarian activity before the age of 40,associated with menstrual disturbance,raised gonadotropins and low estradiol.It is also an important cause of infertility and harmful to women’s life quality in all aspects including physical,psychological and social with long-term health risks.How to evaluate and improve patients’ health-related quality of life(HrQoL)has become a growing concern in reproductive and gynecological academic circles in both China and abroad.However,at present,there are few HrQoL qualitative studies focus on POI patients,especially in China,which cannot provide enough evidence to the selection of the evaluation instruments according to patients’perspective in clinical research;besides,in terms of treatment,there are still many limitations and disadvantages in western medicine,especially in improving patients’HrQoL.However,Traditional Chinese Medicine(TCM),especially acupuncture,is drawing more attention in the treatment of POI.Clinical and experimental studies have shown that acupuncture has positive effects on improving ovarian function,and on the improvement of HrQoL in many other diseases.Therefore,it is of great significance to carry out the mixed method research to explore HrQoL on POI patients in Chinese population,and to select suitable evaluation instruments to evaluate the treatment effect and advantages of acupuncture,which is also in line with the idea of "holistic view"and "people-oriented" in TCM.AimTo investigate HrQoL of patients with POI,and select the most suitable evaluation instruments in patients’ perspective from all instruments that currently used in clinical research.To evaluate the treatment effect of acupuncture on ovarian function and HrQoL of patients with POI.This preliminary study may benefit the development of a disease specific questionnaire and future multi-centered,large sample clinical research.Method1.Using systematic review and Meta-analysis.Data sources:PubMed,Embase,Web of science,CNKI,and CQVIP,searched from inception until June 2018.The search strategy was a combination of medical(e.g.POI),subjective(e.g.well-being)and methodological(e.g.ques-tionnaires)keywords.PRISMA guidelines were used to assess outcome data quality/validity by one reviewer,verified by a second reviewer.Risk of bias within studies was evaluated.A Meta-analysis compared HrQoL in patients and non-patients.Due to measurement differences in the studies,the effect size was calculated as standard mean difference.2.Using the focus group study.The semi-structured interview was conducted to investigate all dimensions of HrQoL of POI patients,including the whole process of experiencing diagnosis,self-cognition and treatment,the physical,psychological,social/family environmental impact brought by POI disease,as well as seeking treatment and the change of life plan.The card sorting of domains and key words were analyzed quantitatively.An expert group was established to carry out quality control in the whole process of the interview research.All interviewees were trained to reduce the possible bias.The qualitative results were analyzed using graneheim&lundmatn(date)method,so as to determine the HrQoL themes.The quantitative results were analyzed by frequency and sequence,so as to order the importance of the selected dimensions and keywords.After experts’ discussion,the most suitable instruments were recommended.3.A before-after(pre-post)study was carried out to evaluate treatment effect.The patients were recruited from five centers in China from July 2019 to November 2019,who meet the POI diagnostic criteria and sign the informed consent.The patients were divided into two groups according to whether they have strong fertility concern or not.The ovarian function indexes were measured before and after treatment,including follicle stimulating hormone(FSH),luteinizing hormone(LH),FSH/LH,estradiol(E2),antral follicle count(AFC)and multi time point evaluation of HrQoL instruments:fertility group(A):Menopause quality of life scale(MENQoL)and Fertility quality of life scale(FertiQoL);non-fertility group(B):MENQoL and World Health Organization Quality of Life(WHOQoL-BREF).The safety of acupuncture was also observed.Results1 Systematic review and Meta-analysisWe identified 6869 HrQoL studies.24 geographically diverse studies met inclusion criteria,dated from 2006,using 23 questionnaires.5 articles were related to treatment evaluation,and 19 articles discussed the investigation and comparison of the aspects of HrQoL in POI patients.The Meta-analysis included six studies with 645 POI participants(age 33.3±5.47)and 492 normal-ovarian control subjects(age 32.87± 5.61).Medium effect sizes were found for lower overall HrQoL(pooled SMD=-0.73,95%CI-0.94,-0.51;12=54%)and physical function(pooled SMD=-0.54,95%CI-0.69,-0.39;12=55%).Heterogeneity was investigated.Effect sizes varied for sexual function depending on the measure(SMD=-0.27 to-0.74),overall HrQoL(SF-36)had the largest effect size(-0.93)in one study.The effect sizes for psychological and social HrQoL were small.26 different instruments were currently used in clinical research.It included 2 generic HrQoL questionnaires,1 functional well-being questionnaire,14 psychological aspects questionnaires,1 life event questionnaires,3 sexual function questionnaires,3 disease or symptom specific questionnaires,1 POI specific questionnaires and 1 preserved social support questionnaires.2 Focus group studyThe interview included 20 POI patients,15 in the fertility group,3 groups in total,5 in the non-fertility group,1 group in total.After coding process,339 meaningful units were formed with 7 themes:1)suffering due to infertility;2)menopause change;3)premature aging;4)changes in life plan and attitude of future;5)changes in relationships with others;6)negative emotions;7)coping and needing.In terms of domains,50%of patients concerned physical domain was most affected.45%thought that psychological domain was the most affected,and 5%chose social dimension as the most influential dimension.According to the frequency,the top ten key words were:pressure,fertility,anxiety,premature aging,sense of failure,social relations,fatigue,depression,body shape change,menopause symptoms.In addition,more than half of the patients chose fear,sexual experience,sleep problem,purpose on life,forgetfulness,husband and wife relationship,vitality,hair loss and acceptance.In the physical domain,there are 14 key words,including fatigue,premature aging,body shape change,menopausal symptoms,fertility,sleep problem,hair loss,sexual experience,etc.In the psychological domain,there are 19 key words,including pressure,anxiety,depression,fear,sense of failure,vitality,self-esteem,purpose on life,acceptance,loneliness,etc.In the social dimension,there are 13 key words,including social relationship,husband and wife relationship,mother-in-law relationship,acceptance,purpose on life,etc.For patients with fertility needs,MENQoL and FertiQoL were selected;for patients without fertility needs,MENQoL and WHOQOL-BREF were selected.3 Clinical research3.1 Participants and baselineIn this study,50 patients were included in the study and 40 patients were included in the data analysis.31 patients were in the fertility group and 9 patients were in the non-fertility group.24 patients only used acupuncture and 16 patients combined with hormone replacement therapy(HRT).No serious adverse events occurred in the whole treatment process.3.2 Ovarian function indicatorsCompared with before treatment,FSH and LH decreased significantly after treatment(P<0.05).FSH/LH decreased after treatment,but the difference was not statistically significant(P>0.05).E2 increased after treatment,the difference was statistically significant(P<0.05).AFC increased after treatment,the difference was not statistically significant(P>0.05).Subgroup analysis showed that patients combined with HRT had higher FSH and AFC values and lower LH,FSH/LH and E2 values after treatment,but the difference between the two groups was not statistically significant(P>0.05).3.3 MENQoLCompared with visit 1,the scores of visit 2,visit 3 and visit 4 were changed significantly(P<0.05),but there was no significant difference between visit 2 and visit 3,visit 2 and visit 4,visit 3 and visit 4(P>0.05).The score change of sexual life was not significant(P>0.05).The psychological domain of visit 4 was significantly improved compared with visit 1,the difference was statistically significant(P<0.05),but there was no significant difference between visit 2,3 and visit 1,visit 3,4 and visit 2,visit 3 and visit 4(P>0.05).Physical domain of visit 3,4 and visit 1 were significantly improved,the difference was statistically significant(P>0.05),visit 2 and visit 1,visit 3,4 and visit 2,visit 3 and visit 4 had no significant change(P>0.05).The total score of visit 3 and 4 was significantly improved compared with visit 1,the difference was statistically significant(P<0.05),but there was no significant difference between visit 2 and visit 1,visit 3,4 and visit 2,visit 3 and visit 4(P>0.05).There was no significant difference between whether combined with HRT(P>0.05).There was no significant difference between whether the patients had fertility needs(P>0.05).29 items were compared,the results showed that items 1-6,8,9,11-20,22-24,27,28 changed significantly,the difference was statistically significant(P<0.05).The other items decreased,but not significantly(P>0.05).3.4 FertiQoLThe results showed that the scores of most dimensions increased with the treatment process,but only the emotional domain improved significantly in visit 4 compared with visit 1(P<0.05).The other domains were not significant changed(P>0.05).There was no significant difference between the two groups whether combined with HRT(P>0.05).Compared with visit 1 and visit 4,the changes of items Q1,8,9,16 and 17 were significant(P<0.05).There was no significant difference in other items(P>0.05).3.5 WHOQoL-BREFThe results showed that although there were changes among the domains,the changes were not significant(P>0.05).Compared with visit 1 and visit 4,the changes of items 1,8 and 22 were significant(P<0.05).Although there were changes in other items,they were not obvious(P>0.05).3.6 Safety analysis4 patients appeared needle sticking,7 patients appeared subcutaneous ecchymosis during treatment.All patients had no serious adverse reactions.Conclusion1.All domains of HrQoL in POI patients were decreased,mainly including suffering from infertility,menopause changes,negative emotions and other seven aspects.Among them,the physical change is the most important aspect,while the psychological dimension involves a wider range.At present,MENQoL,FertiQoL and WHOQoL-BREF are the PRO scales which are more suitable for patients’ feelings,and are recommended for clinical research.2.Clinical research shows that acupuncture can improve ovarian function(i.e.reduce FSH,LH and E2 values)and HrQoL of patients with POI.It can improve HrQoL of patients by improving multiple domains of menopause related quality of life and fertility related emotional changes,especially in alleviating various physical symptoms caused by low estrogen and extensive emotional regulation.There was no significant difference in ovarian function and HrQoL between acupuncture treatment only and combined with HRT.No significant adverse reactions occurred.It is proved that acupuncture to be a safe and effective method for ovarian function and health-related quality of life of POI patients. |
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