LIU Baoyan[Corresponding author: LIU Baoyan, E-mail: baoyanjournal@163.com (BL)], GAO Deqiang1, HE Liyun1, FANG Yigong2, YANG Xingyue 3, Lin Luo1, LIU Yan1

(1.Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China; 2.Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China;3.Beijing University of Chinese Medicine, Beijing, China)

Premature ovarian insufficiency(POI), is the loss of ovarian function before age 40 ^[1], characterized by amenorrhoea for at least 4 months, elevated gonadotrophins and sex steroid deficiency. ^[2]

POI affects 1-2% of women younger than 40, it can be caused by genetic, metabolic, infectious, autoimmune, and iatrogenic dysfunctions such as surgery, chemotherapy, and radiotherapy. ^[3] Symptoms of POI include hot flushes, night sweats, depression, irritability, nervousness, loss of libido, lack of concentration, weight gaining, dry skin, vaginal dryness etc. ^[4] POI may result in remarkable impacts on fertility, physical and psychological wellbeing. POI patients have 5%-10% chance of spontaneous pregnancy. ^[5] Oocyte donation and reproductive techniques have been offered as alternatives for those who want to have a family, yet the result is not satisfactory. ^[6] Long-term sequelae of POI include increased cardiovascular events, decreased cognitive function, increased risk of dementia, devastating psychological effects, increased all-cause mortality, decreased life expectancy. ^[7-10] The first line treatment is hormone replacement treatment (HRT), if contraindications avoided, HRT is indicated to reduce the risk of cardiovascular disease, osteoporosis, and urogenital atrophy. ^[11] Unfortunately, menopausal women who accepted HRT were found to be associated with increased risks of heart attacks, strokes, breast cancer. ^[12-13] Controversies exist when it comes to optimal HRT for POI. ^[1,11] Evidence is limited for large-scale long-term randomized prospective HRT studies. Also, risks of long-term use of HRT are still unknown. 

Other therapy options include alternative and complementary treatment and behavioral changes, such as stop smoking, regular weight bearing excises. ^[1] Acupuncture, as an integral part of traditional Chinese medicine, has been practiced widely around the world, ^[14] has long been used for treating symptoms which are similar to menopause, little or even no side effects were reported. Acupuncture has been found to be effective in relieving hot flashes in bilaterally ovariectomized Chinese women ^[15]_. A recent published systematic review indicates that acupuncture could be effective in restoring menstruation and improving hormone levels. ^[16] Zheng et al. ^[17] found that acupuncture could improve pregnancy outcomes in women undergoing in vitro fertilization (IVF).

However, previous acupuncture studies in treating POI are small trails which may not well characterize the general responses. ^[18,19] Ovarian functions in POI patients may be varying and unpredictable, follow-ups of these trails are not relatively not long enough. ^[5,20] Though randomized controlled trial can serve as high level evidence, acupuncture, like other interventions, used in randomized controlled trial often considerably differ from how it is practiced in real clinical settings. ^[21] It is not uncommon that disparities exist for results between intervention in actual clinical practice and clinical trials. ^[22,23]POI patients who are eager to prepare themselves for pregnancies or assisted reproductive technology may not agree with being located to sham acupuncture intervention. Thus, high quality observational research is needed to explore comprehensive management of acupuncture in POI patients.

Patient registry is one form of observational study in which data are collected to evaluate specified outcomes for a particular disease, condition, or exposure. Patient registry can be used for predetermined clinical, scientific, or policy purposes. ^[24] Compared with cohort study, patient registry goes far for being more flexible in terms of scope and focus of the data collection activity, registry may be adapted over time to address additional needs. By POI registry, we can observe long-term response, safety, and effectiveness of acupuncture therapy in a real-world view of clinical practice.

Recently, international patient registry is gaining its popularity for growing interests in certain diseases, such as kidney diseases, acute coronary syndrome, acute aortic dissection etc. ^[25-27] However, running an international registry can be difficult owing to various challenges relating to data collection, entry, and analysis. ^[28] To our knowledge, meaningful attempts have been made on patient registry for POI, ^[29-30] no patient registry for acupuncture therapy about a certain disease has been found by now, which could be even more complex and challenging. 

First, acupuncture itself is complex intervention whose treatment outcome may be affected by syndrome differentiation, acupoints selection, treatment sessions, frequencies, patient-practitioner interaction, and patient expectation, ^[31-33] yet there is no consensus for acupuncture protocol in treating POI. To make it worse, there is also no agreement on how to choose patient-reported outcomes. ^[34]

Second, in real clinical settings, variations and confounding factors, such as combined intervention^[35] and lifestyles, cannot all be detailed and documented, which make it more difficult to measure how they influence the effectiveness of acupuncture. The etiology of POI is not clear in most cases, making the design of data set more complex. ^[1]

Third, global data set management is a practical challenge. It is about data quality and interoperability, about data ownership and privacy, about physician and patient recruitment and retention in bdifferent health systems and cultures, about adverse event detection, processing, and reporting. ^[24]

However, there’s ample reason to push forward. For one reason, even though there are variations and deficiencies in data collection and analysis, collaboration of global experts can minimize the limitations, help deepen our understanding of the POI courses and therapeutic effects with or without acupuncture. For another, we may uncover treasures buried in real world practice, for example, the role of acupuncture in fertility of POI.

We have now established expert panels in China of which experienced acupuncture professionals, endocrinologists and gynecologist are included. They contributed to complete our online registry http://www.amreg.org:8082/v3, more than 200 POI patients have enrolled our study. In the future, more international professionals are needed and welcomed to participant to the study. By adequate communication, consensus, and collaboration, we can optimize regimen of acupuncture to do more for POI patients.   

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