| ObjectiveOvarian reserve is the capacity of the primordial follicles in the ovarian cortex to develop into fertilized oocytes. It is usually evaluated by the number of follicles left in the ovarian cortex and the quality of oocytes to reflect women's fertility. With the continuous development of in vitro fertilization and embryo transfer and its derivative technology, many infertile couples pregnancy by assisted reproductive technology, but the assisted reproductive technology still faces a series of challenges, which improve the ovarian reserve function decline in patients with clinical efficacy and pregnancy rate is still lack of effective and safe method, is a problem for clinicians.In the past few years, studies have demonstrated that the transcutaneous electrical acupoint stimulation (TEAS) used for the treatment of patients undergoing IVF-ET can improve egg quality and increase pregnancy rate. TEAS is an acupuncture point stimulation method based on electrical stimulation signal instead of traditional hand-twisted mechanical stimulation. It quantitatively controls stimulation time and stimulus intensity of acupuncture therapy, avoids the pain caused by acupuncture and topical skin tissue injury, and hence is easily accepted by patients. TEAS has been widely used in clinical treatment and research.Our study aimed at investigating the effect of TEAS on the ovarian reserve of patients undergoing IVF-ET with decreased ovarian reserve, and hope to seek a safe and effective treatment for these patients.Methods 1?Subjects investigatedA total of 240 patients with decreased ovarian reserve who underwent IVF-ET were enrolled from the Reproductive Center in Second Affiliated Hospital of Shandong Traditional Chinese Medicine University (China) between July 2012 and July 2013. The patients ranged in age from 26 to 47 years and had an infertility duration of 1-15 years. In all the patients, infertility was due to tubal-induced gamete transport barriers. The patients were grouped into Han's TEAS treating group (TES group, n=60), false Han's placebo group (FHP, n=60), and artificial endometrial cycle treatment group (AEC, n=60). Meanwhile, patients unwilling to receive TEAS or artificial cycle treatment were selected as control group (CON, n=60). The entire study was approved by the Ethics Committee of the Second Affiliated Hospital of Shandong Traditional Chinese Medicine University and all the participants signed informed consent.2?Inclusion and exclusion criteria2.1 Inclusion criteriaOwing to the lack of a standard definition of ovarian reserve, the decrease of ovarian reserve in patients was assumed based on previous reports if they satisfied at least one of the following conditions:(1) basal follicle-stimulating hormone(FSH) levels?10IU/L or follicle-stimulating hormone/luteinizing hormone (FSH/LH) ratio >3.6 detected at least twice, (2) AFC in bilateral ovarian?5; (3)age?35 years old; (4) a history of pelvic surgery;(5) infertility was due to tubal-induced gamete transport barriers.2.2 Exclusion criteriaPatients with endometriosis, and intracytoplasmic sperm injection for male factor infertility were excluded from this study.3?Therapeutic methods3.1 Artificial endometrial cycle treatment for patients in the AEC groupPatients induced by artificial cycle took oral tablets of estradiol valerate (Progynova,1 mg/tablet, Bayer Pharmaceutical Company) at a dose of 2 mg/day for 21 days from the 5th day of the menstruation. Ten days prior to the last dose, the patients received dydrogesterone tablets (Duphaston,10 mg/tablet, Abbott Healthcare Products B.V.) at a dose of 20 mg/day for three cycles.3.2 TEAS treatment for patients in the TES groupAfter the menstrual cycle, patients in the TES group were stimulated by HANS at a frequency of 2 Hz, and treatment was interrupted prior to the next menstrual cycle (a total of three courses). The electrode patch of Han's device (Medical Technology Co., Ltd. Nanjing Jisheng) was affixed to the acupoints enlisted above. Treatment began at a frequency of 2 Hz and a tolerable strength of 20-25 mA; it lasted for 30 minutes and was given once a day. After three courses, the treatment continued during the ovulation cycle until the day of egg retrieval.3.3 Treatment for patients in the FHP groupThe false HANS is a scientific instrument similar to true HANS. However, regardless of electric current on the displays, its output current was stable at 5 mA. During the treatment, the electric current was turned on for 3 seconds and paused for 7 seconds. So the patients experienced alternate feelings of sensation and numbness in the acupoints. The false HANS worked as a placebo but not as a treatment, which has been confirmed in a smoking cessation trial of Singapore. False HANS was used for patients in the FHP group by the same method used for those in the TES group.4?Main test indexes4.1 Ultrasonic examination indexesBefore treatment, the second day of the menstrual cycle, the indicators of AFC, ovarian artery resistance index (RI), ovarian artery pulsatility index (PI), and systolic/diastolic flow velocity ratio (S/D) were measured, and the parameters were repeated after 3 cycles.4.2 Detection of endocrine hormonesBefore treatment, the second day of the menstrual cycle, the indicators of basal estradiol (E2) level, basal FSH level, basal luteinizing hormone (LH) level, AMH level, FSH/LH ratio, were measured, and the parameters were repeated after 3 cycles.4.3 Collection of clinical indicatorsThe average Gn dosage (total Gn dosage used in hyperstimulation ovulation (unit) /the number of patients undergoing controlled ovarian hyperstimulation) and average duration of Gn administration (total days using Gn in hyperstimulation ovulation/the number of patients undergoing controlled ovarian hyperstimulation) were recorded.After oocyte retrieval, the number of oocytes, FSHR protein extraction,fertilization rate, cleavage rate,clinical pregnancy, and miscarriage rate were calculated.Resuits1?The comparison of the situation of each group of patients in the treatmentDuring the treatment,6 patients from the AEC group,4 from the FHP group and 4 from the TES group withdrew from the study due to discontinued or intermittent medication. There was no significant difference (all P values>0.05) in age, duration of infertility, cause of infertility, body mass index, AFC prior to treatment, E2 values, FSH values, basic LH values, AMH level, RI, PI, and S/D among the four groups. In addition, patients with a history of pelvic surgery (oophorocystectomy or partial oophorectomy) were evenly distributed among groups.2?Comparison of therapeutic effect of the treatment groups2.1 Comparison of ultrasonic testing indexes of three groups before and after treatment in treatment groupAfter the treatment, AFC was increased (P<0.05) in the TES and AEC groups. These indicators did not differ (P>0.05) prior to and post treatment in the FHP group. RI, PI, and S/D were not significantly different (P>0.05) prior to and post treatment in the TES, FHP, and AEC groups, and between the TES and AEC groups post treatment.2.2 Comparison of basal endocrine hormones before and after treatment in three groups of treatment groupsAfter the treatment, AMH level was increased whereas E2 level, FSH level, and FSH/LH ratio were significantly decreased (P<0.05) in the TES and AEC groups. These indicators did not differ (P>0.05) prior to and post treatment in the FHP group.2.3 Comparison of clinical indexes of four groups of patientsThe average Gn dosage and average duration of Gn administration were lower in the TES and AEC groups than in the CON and FHP groups, and lower in the TES group than in the AEC group (P<0.05). The patients in the TES, FHP, and AEC groups were similar (P>0.05) in their clinical indicators and basic endocrine indicators. After treatment, the number of oocytes and the average number of embryos transferred were higher (P<0.05) in the TES and AEC groups than in the CON and FHP groups, but not significantly different (P>0.05) between the TES and AEC or CON and FHP groups. Clinical pregnancy in the TES group was markedly higher (P<0.05) than the other three groups. No significant difference (P>0.05) was found in fertilization rate, cleavage rate, and high-quality embryo rate among the four groups.3?FSHR protein expression in granulosa cells of the patients in four groupsThe FSHR protein expression was significantly higher (P<0.05) in the TES and AEC groups than in the CON and FHP groups, and higher in the TES group than in the AEC group.Conclusions1?TEAS could increase the number of antral follicles in patients with decreased ovarian reserve, and could improve the AMH levels, decrease the basal E2 level? basal FSH leveh basal FSH/LH ratio. So it could improve the ovarian function of patients.2?TEAS could reduce the dose and duration of gonadotropin in the treatment of IVF, increase the number of oocytes retrieved and improve the clinical pregnancy rate in the patients with decreased ovarian reserve in IVF. So it could reduce the economic burden of patients, improve the therapeutic effect of IVF.3?The effect may be related to the increase of FSHR expression in the treatment of TEAS, which makes the follicle more sensitive to the stimulation of the exogenous FSH.4?Compared with the traditional acupuncture, TEAS could avoid the adverse reaction of skin injury, infection, treatment etc.. The advantage is that it can continue to stimulate, quantitative stimulation, easy to operate, no pain, and easy to be accepted by patients. As a treatment method with no obvious adverse reaction, it could improve the ovarian function of patients and improve the therapeutic effect of IVF.So TEAS can be popularized and applied in the patients with decreased ovarian reserve in IVF-ET. |
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