Clinical Effects of the Follicular Phase Long Regimen and Luteal Phase Long Regimen on Ovulation Induction in IVF-ET Treatment: A Meta-Analysis

Objective:To systematically evaluate the clinical effects of the follicular phase long regimen and the luteal phase long regimen on ovulation induction in IVF-ET treatment.Methods:Databases including PubMed,Embase,Cochrane Library,CNKI,Chinese Biomedical Literature(CBM),VIP,Wanfang,and others were searched up to January 2021.Clinical studies on ovulation induction using the follicular phase long regimen and luteal phase long regimen in IVF-ET treatment were identified.Literature screening,data extraction,and quality evaluation were conducted based on inclusion and exclusion criteria.Meta-analysis was performed using RevMan 5.3 software.Results:After screening,a total of 11 studies were included,comprising 21,544 patients:9,974 in the follicular phase long regimen group and 11,570 in the luteal phase long regimen group.The meta-analysis results were as follows:(1)The number of Gn days and the total amount of Gn in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05);(2)The number of eggs obtained in the follicular phase long regimen was higher than that in the luteal phase long regimen(P<0.05).There were no significant differences in the rate of embryo optimization and cycle cancellation between the two groups(P>0.05);(3)The embryo implantation rate and clinical pregnancy rate in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05),while the abortion rate in the follicular phase long regimen was lower than that in the luteal phase long regimen(P<0.05).Conclusion:Compared to the luteal phase long regimen,the follicular phase long regimen involves more Gn days and a higher total amount of Gn.The optimal embryo rate and cycle cancellation rate were similar between the regimens,but the follicular phase long regimen resulted in more eggs,significantly improved the implantation and clinical pregnancy rates,and reduced the abortion rate.However,these conclusions require further validation through more multicenter,large-sample RCT studies.

Effect of Mitochondrial Function of Ovarian Granulosa Cells on In Vitro Fertilization and Embryo Transfer Outcomes in Obese Polycystic Ovary Syndrome Patients

Objective:To investigate the effect of abnormal ovarian granulosa cell metabolism on in vitro fertilization and embryo transfer(IVF-ET)outcomes in obese polycystic ovary syndrome(PCOS)patients.Methods:Patients with PCOS who met the study criteria were screened according to the inclusion criteria.A total of 32 patients with obese PCOS were recruited into the study group,and 39 patients with non-obese PCOS were recruited into the control group.The general data(age,body mass index,and years of infertility),insulin resistance index(HOMA-IR),follicle-stimulating hormone(FSH),luteinizing hormone(LH),granulosa cell mitochondrial function,and IVF-ET outcome of patients in the study group and control group were retrospectively analyzed.Results:The differences in age and years of infertility between the study group and the control group were insignificant(P>0.05),and the body mass index(BMI)of the study group and control group was 30.5±1.24 kg/m2 and 22.3±1.12 kg/m2,respectively,in which the difference was statistically significant(P<0.05);the HOMA-IR of the study group was significantly higher than that of the control group(P<0.05);the reactive oxygen species(ROS)in the study group was significantly higher than that in the control group(P<0.05),and the ATP content in the study group was significantly lower than that in the control group(P<0.05);comparing the FSH and LH levels between the two groups,the difference was not statistically significant(P>0.05);the rate of IVF-ET failure was significantly higher in the study group than in the control group.Conclusion:PCOS is a complex endocrine disorder,and obesity is one of the independent risk factors for the development of PCOS.

Effect of Progestin-primed Ovarian Stimulation Protocol on Outcomes of Aged Infertile Women Who Failed to Get Pregnant in the First IVF/ ICSI Cycle： A Self-controlled Study

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol （PPOS） in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn＇t get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol （non-PPOS group）, and underwent PPOS protocol （PPOS group） in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer （FET） in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone （bFSH）, antral follicle count （AFC）, duration and total dosage of gonadotropin （Gn）, number of oocytes retrieved, intracytoplasmic sperm injection （ICSI） rate, fertilization rate, and cycle cancellation rate between the two groups （P〉0.05）. However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group （P〈0.05）. By the end of April 2017, 62 FET cycles were conducted in PPOS group. The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%, respectively. In conclusion, PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ ICSI-ET cycles.

Reproductive Outcomes in Women with Prior Cesarean Section Undergoing In Vitro Fertilization:A Retrospective Case-control Study

The impact of prior cesarean section（CS） on the pregnancy and neonatal outcomes of in vitro fertilization and embryo transfer（IVF-ET） was investigated. A retrospective analysis was performed on 144 patients with prior CS between January 2013 and December 2015. The pregnancy, delivery, and neonatal outcomes of patients who had previous CS delivery and received IVF-ET were analyzed. The control group comprised 166 patients who had only previous vaginal delivery（VD） and received IVF-ET during the same period. The results showed that the basal follicle stimulating hormone level, estradiol level on human chorionic gonadotropin（h CG） day, gonadotrophin dosage, duration of stimulation, retrieved oocytes, fertilization rate, high-quality embryo rate, multiple birth rate, abortion rate and ectopic pregnancy rate had no significant difference between the two groups（P〉0.05）. The pregnancy rate（40.28% vs. 54.22%） and implantation rate（24.01% vs. 34.67%） were significantly lower（P〈0.05）, and the ratio of embryo difficulty transfer（9/144 vs. 0/166） was significantly higher in CS group than in VD group. The risk of pernicious placenta previa and postpartum hemorrhage in twin deliveries was significantly increased in CS group as compared with that in VD group（P〈0.05）, and gestational age and neonatal birth weight were significantly reduced in twin deliveries as compared with singleton deliveries in both groups（P〈0.05）. It was suggested that the existence of CS scar may impact embryo implantation and clinical pregnancy outcome, and increase the difficulty of ET. We should limit the number of transfer embryos to avoid multiple pregnancies and strengthen gestational supervision in patients with cesarean scar.

Post-salpingectomy interstitial heterotopic pregnancy after in vitro fertilization and embryo transfer:A case report

BACKGROUND Heterotopic pregnancy(HP)refers to the coexistence of ectopic pregnancy and intrauterine pregnancy.Salpingectomy is proposed as a pretreatment before in vitro fertilization and embryo transfer(IVF-ET)to reduce the risk of HP.HP after IVF-ET occurs in women who had already underwent bilateral salpingectomy,even though it is extremely rare.CASE SUMMARY A case of a 29-year-old woman with recurrent interstitial HP after IVF-ET following salpingectomy is presented.The main symptom was a sudden and worsening pelvic pain.Physical examinations revealed signs of peritoneal bleeding and irritation with stable vital signs.Transvaginal ultrasound showed a live intrauterine pregnancy and another live embryo with cardiac activity in the left cornu extending beyond the lateral edge of the uterus.Her hemoglobin concentration was 8.0 g/dL,and serum human chorionic gonadotropin value was 171116.9 mIU/mL.With the diagnosis of ruptured HP with internal bleeding,an emergency laparoscopic resection of left cornu was performed.The interstitial pregnancy was removed with caution to protect the intrauterine pregnancy.After the surgical treatment,the intrauterine pregnancy continued with no complications.A healthy baby was delivered by caesarean section at 39 wk.Outcomes of another three cases are further summarized.CONCLUSION Post-salpingectomy HP is a rare but challenging condition.Surgical treatment is preferred in the case with a viable intrauterine pregnancy.

Comparison between a GnRH Agonist and a GnRH Antagonist Protocol for the Same Patient Undergoing IVF

In order to compare GnRH agonist with antagonist protocol for the same patient during controlled ovarian stimulation cycles, the in vitro fertilization and embryo transfer （IVF-ET） outcome was retrospectively studied in 81 patients undergoing 105 agonist protocols and 88 antagonist protocols. The results showed that there was no statistically significant difference in duration of ovarian stimulation, number of ampoules, oocytes retrieved, serum estradiol （E2） and progesterone （P） levels, thickness of endometrium, the zygote- and blastocyst-development rate between GnRH agonist and antagonist protocols （P〉0.05）. High quality embryo rate was higher in antagonist protocols, but there was no significant difference between two protocols. Implantation rate and clinical pregnant rate were significantly higher in antagonist protocol （15.82% and 30.26%, respectively） than in agonist protocol （5.26% and 10.64% respectively （P〈0.05）. It was concluded GnRH antagonist protocol probably improved the outcome of pregnancy of older patients with a history of multiple failure of IVF-ET in a GnRH protocol.

A woman by successful IVF and caesarean delivery without complications in autosomal dominant centronuclear myopathy

Autosomal-dominant centronuclear myopathy is a rare hereditary disease in adolescents,mainly involving the distal muscles of the lower extremity.It is extremely rare in pregnancy.This study presented a case of a woman by successful IVF and caesarean delivery without complications in autosomal dominant centronuclear myopathy.This report also reviewed the clinical spectrum of CNM and its management,which resulted in the delivery of a healthy infant.It is important that the clinician has a clear understanding of the clinical spectrum of CNM,the available methods for perinatal diagnosis,and optimal antenatal care.A multidisciplinary team approach is emphasized,with specific reference to the method of analgesia and anesthesia during labor and route of delivery.

Double Pulmonary Embolism and Left Common Iliac Vein Thrombosis after in vitro fertilization and embryo transfer： a Case Report

This article discusses the mechanism, diagnosis, and treatment of a case of double pulmonary embolism and left common iliac vein thrombosis following in vitro fertilization （IVF） and embryo transfer （ET） to arouse vigilance for unexpected thrombosis after ovarian hyperstimulation and to serve as a clinical reference of this condition. This paper reports the case of a woman with double pulmonary embolism and left common iliac vein thrombosis after IVF-ET and the successful management of this condition. The woman had primary infertility, and underwent IVF-ET with 14 ooeytes recovered and two embryos transferred. The patient suffered breathing difficulty 17 days after the ET, and was hospitalized 6 days later as her condition had exacerbated. Computed tomographic （CT） angiography of pulmonary arteries showed double pulmonary embolism, left common iliae vein thrombosis, abnormal density shadow in uterine appendages, and ascites. A healthy baby boy and girl were safely delivered by Caesarean section after successful treatment. Thrombosis after IVF-ET is an uncommon but life-threatening complication and concurrent pulmonary embolism is even rarer. It is suggested that careful thrombosis risk assessment be taken before therapy and particular attention be paid to patients with special body constitutions to develop thrombosis. Whenever patients experience breathing difficulty after IVF-ET, it is strongly advised to examine the possibility of pulmonary embolism. The main treatments for thrombosis are anticoagulant therapy by low-molecular-weight heparin and thrombolysis by urokinase.

Acupuncture for Infertility:Is It An Effective Therapy?

Acupuncture has been used to treat infertility extensively, including ovulatory dysfunction, in vitro fertilization and embryo transfer （IVF-ET）, and male infertility. This review summarizes the recent studies which investigated the role of acupuncture in infertility. In conclusion, most of the existing studies suggest a positive effect of acupuncture in infertility treatment. Firstly, acupuncture may improve ovulation by modulating the central and peripheral nervous systems, the neuroendocrine and endocrine systems, the ovarian blood flow, and metabolism. Secondly, acupuncture can improve the outcome of IVF-ET, and the mechanisms may be related to the increased uterine blood flow, inhibited uterine motility, and the anesis of depression, anxiety and stress. Its effect on modulating immune function also suggests helpfulness in improving the outcome of IVF-ET. Finally, the studies suggest that acupuncture plays a positive role in male infertility, the mechanism of which is not yet clear. Even though a positive effect of acupuncture in infertility has been found, well-designed multi-center, prospective randomized controlled studies are still needed to provide more reliable and valid scientific evidence. Furthermore, it is urgent and necessary to clarify the mechanism of acupuncture for infertility.

Pregnancy outcomes after fertility preservation in women with endometrial carcinoma and atypical endometrial hyperplasia:A systematic review and meta-analysis

Objective:The objective of the study was to compare the effects of assisted reproductive technology(ART)and spontaneous pregnancy on pregnancy outcomes in women with endometrial carcinoma(EC)and atypical endometrial hyperplasia(AEH)following fertility-sparing treatments.Methods:Relevant studies published through July 2020 were identified from PubMed and Web of Science literature searches.The pregnancy outcomes of ART and spontaneous pregnancy were summarized and compared for women with complete remission of EC/AEH after fertility-sparing treatments.A subgroup analysis was performed based on whether patients had received in vitro fertilization and embryo transfer(IVF-ET)treatment.The complete remission and recurrence rates of EC/AEH following fertility-sparing treatments were estimated.The effect of pregnancy on recurrence rates of EC/AEH was also calculated.Results:Sixteen observational studies reporting pregnancy outcomes or recurrence with ART or spontaneous pregnancy for women with EC/AEH after fertility-sparing treatments were included.The complete remission rate of EC/AEH was 81.5%(95%CI,78%–85%).Compared with spontaneous pregnancy,the pregnancy rate of ART was significantly higher(66.8%vs.43.7%,OR=2.64,95%CI 1.71–4.05,P<0.00001,I^(2)=14%).Subgroup analysis showed that the pregnancy rate of IVF-ET was significantly higher than that of spontaneous pregnancy(62.7%vs.35.1%,OR=2.85,95%CI 1.44-5.63,P=0.003,I^(2)=29%).The live birth rate of ART was significantly higher than that of spontaneous pregnancy(75.3%vs.47.8%,OR=3.96,95%CI1.76-8.77,P=0.0009,I^(2)=45%).The recurrence rate of EC/AEH was 31%(95%CI 24%–39%).Clinical pregnancy could reduce the recurrence rate of EC/AEH,but there was no significant evidence of an association.Conclusions:ART,especially IVF-ET,could significantly improve pregnancy outcomes in women with EC/AEH receiving fertility-sparing treatments.Following complete remission,ART treatment might be a better option for women with EC/AEH than spontaneous pregnancy.

Effect of electroacupuncture on oocyte quality and pregnancy of patients with PCOS undergoing in vitro fertilization and embryo transfer

Objective To observe the impacts of electroacupuncture （EA） on oocyte quality and pregnant outcome for the patients with polycystic ovary syndrome （PCOS） undergoing in vitro fertilization and embryo transfer （IVF-ET） and explore its potential mechanism. Methods Sixty-six patients with PCOS and undergoing IVF-ET were divided into two groups randomly, including an observation group （34 cases） and a control group （32 cases）. Ethinylestradiol and cyproterone acetate tablets and gonadotropin-releasing hormone agonist were administered for long-program superovulation in either group. In the observation group, the intervention of EA was applied to Guānyuán （关元 CV 4）, Zhōngjí （中极 CV 3）, Sānyīnjiāo （三阴交 SP 6）, Zǐgōng （子宫 EX-CA 1） and Tàixī （太溪 KI 3） additionally for 30 min, once daily, 1 menstrual cycle before controlled ovarian hyperstimulation （COH） and during COH. The pregnant outcome, evaluation of kidney deficiency syndrome, blood hormone level on the day of human chorionic gonadotropin injection and the concentrations of stem cell factor （SCF） in the serum and follicular fluid on the day of oocyte collection were compared between the two groups. Results The score of kidney deficiency symptoms was reduced remarkably after treatment in either group and the improvement in the observation group was superior to that in the control group （P0.01）. The fertilization rate [（76.25？±？20.33）% vs （66.34？±？15.44）%], cleavage rate [（98.66？±？3.70）% vs （94.47？±？9.45）%] and the rate of high-quality embryos [（60.20？±？22.20）% vs （50.55？±？16.15）%] in the observation group were all superior to those in the control group separately （all P0.05）. Clinical pregnancy rate （46.67%, 14/30） in the observation group was higher than that （37.93%, 11/29） in the control group, but without statistical difference （P0.05）. SCF concentrations in the serum and follicular fluid on the day of oocyte collection in the observation group were higher obviously than those in the control group （both P0.05）. Conclusion Electroacupuncture plays an active role in the pregnant outcomes of PCOS patients undergoing IVF-ET and it can relieve the symptoms of kidney deficiency in terms of TCM and improve clinical pregnant rate. The mechanism is relevant to the overall adjustment of organic endocrinal system and the local micro-environment of ovary and the improvement of oocyte quality through the up-regulation of SCF concentration.

Does human papillomavirus infection do harm to in-vitro fertilization outcomes and subsequent pregnancy outcomes？

Background Some studies suggested that human papillomavirus （HPV） infection could reduce the clinical pregnancy rate and double the spontaneous abortion rate compared with non-infected women after in-vitro fertilization and embryo transfer （IVF-ET）. But some other studies showed there was no difference between HPV infected and non-infected groups of ART outcomes. The role of HPV infection in infertile women undergoing IVF treatments has been a controversial issue which this article attempts to investigate. Methods This is a retrospective analysis of 3880 infertile women undergoing IVF treatment at Peking University Third hospital reproductive medical center in 2008. Patients with abnormal thin-layer preparation cytologic test （TCT） results who underwent fresh cycle embryo transfer were divided into an HPV positive group （n=56） and an HPV negative group （n=56）. The clinical parameters were compared （using Student＇s t-test and chi-squared test）. Univariate and multivariate analyses were taken to see if HPV infection affects the clinical pregnancy rate. Results Of the 3880 cases 157 had TCT abnormality （4.0%）. Of the 149 patients who had HPV test results, 112 women （81.2%） received a fresh cycle embryo transfer. Each group had 56 cases. The patients were of similar age and BMI, basic hormone levels, and infertile factors were similar. The gonadotropin use, oocyte retrieval number, clinical pregnancy rate, abortion rate and newborn condition were all similar between groups. Analyses showed neither HPV infection nor HPV hybrid capture （HC） II results affected clinical pregnancy rate after IVF treatments, but the FSH level did. Conclusion HPV positivity did not appear to impact assisted reproductive technology （ART） success. ＂Extensive treatment＂ for HPV before IVF was not recommended because treatment time will increase age and reduce ovarian function, which will lead to inferior IVF outcomes.

Effects of Transcutaneous Electrical Acupoint Stimulation on Ovarian Responses and Pregnancy Outcomes in Patients Undergoing IVF-ET:A Randomized Controlled Trial

Objective:To evaluate the influence of different transcutaneous electrical acupoint stimulation(TEAS)modes on ovarian responses and pregnancy outcomes in patients with infertility undergoing in vitro fertilization and embryo transfer(IVF-ET).Methods:Two hundred infertility patients undergoing IVF-ET were divided randomly into experimental groups(TEAS groups:E-Ⅰ,E-Ⅱ,E-Ⅲ,and E-Ⅳ,40 cases each group)and a control group(mock TEAS group,40 patients)using the random number method.The patients in the experimental groups received TEAS treatment of 20,30,40 and 50 m A for the E-Ⅰ,E-Ⅱ,E-Ⅲand E-Ⅳgroups,respectively.The control group received a treatment of 5 m A.TEAS was applied at acupoints of Guanyuan(RN 4),Zhongji(RN 3),Sanyinjiao(SP 6),Zigong(EX-CA 1),and Taixi(KI 13),once a day for 30 min each time for a treatment period of 10-13 d.Treatment effect was assessed using the following indicators:endometrial thickness on the 6 th day of gonadotropin treatment(GN6 day),endometrial thickness on the day on chorionic gonadotropin administration(HCG day),number of ovarian follicles on HCG day,number of ova captured,amount of estrogen required for each harvested ova,number of mature ova divided by the total number of ova,percentage of high-quality embryos,and clinical pregnancy.Results:Endometrial thickness in the experimental groups on the HCG day was significantly better than that of the control group after TEAS stimulation(P=0.01).TEAS exhibited a greater impact on the number of ova captured(P=0.003).However,the effect of TEAS stimulation on the high-quality embryo rate and clinical pregnancy in patients was not statistically significant(P>0.05).Conclusions:TEAS is an effective method in improving the ovarian state.When the stimulus intensity was at 40 m A and above,it could be helpful to improve the patient’s endometrial condition and endometrial receptivity and to retrieve more oocytes.(Trial registration No.Chi CTR-TRC-11001780)

Relationship between serum antisperm antibodies and anticardiolipin antibodies and clinical pregnancy outcome in an in vitro fertilization and embryo transfer program

Objective To study the influence of maternal immunological factors on clinical pregnancy outcome in an in vitro fertilization and embryo transfer (IVF ET) program. Methods One hundred and fifty IVF ET treatment cycles from November 1995 to November 1996 were studied. The indication for IVF ET treatment was bilateral blocked tubes. Serum antisperm antibodies and anticardiolipin antibodies were measured using enzyme linked immunosorbent assay (ELISA). Cleavage rate and successful pregnancy rate in relation to antibody status of infertile women after IVF ET treatment were assessed. Results Lower cleavage rate (64.2%±32.1%) was found in 44 cycles of antisperm antibody seropositive women, compared with 84.8%±18.7% in 106 cycles of seronegative women (P<0.05). The clinical pregnancy rate was 31.8% in antisperm antibody positive cycles and 20.8% in negative cycles (P> 0.05). The abortion rates of the two groups were similar (P>0.05). Lower pregnancy rate (9.5%) was found in 21 cycles of serum anticardiolipin antibody positive group, compared with 26.3% in 129 cycles of seronegative women (P<0.05). Of patients with bio chemical pregnancy and no pregnancy, 20.0% and 16.2%, respectively, had seropositive anticardiolipin antibody, compared with 5.6% of patients with clinical pregnancy (P<0.05). Conclusion Serum immunological factors may play a part in clinical pregnancy outcome in IVF ET.

Effect of soothing liver therapy on oocyte quality and growth differentiation factor-9 in patients undergoing in vitro fertilization and embryo transfer

OBJECTIVE:To investigate the effect of Soothing liver therapy on infertile women undergoing in vitro fertilization and embryo transfer(IVF-ET)and to explore its mechanism.METHODS:Fifty-eight women with tubal infertility were randomized into two groups:30 in an experimental group treated with Xiaoyao powder(Shugan)plus gonadotropin-releasing hormone analog(GnRHa)/follicle-stimulating hormone(FSH)/human chorionic gonadotropin(hCG)and 28 in the control group who were treated with GnRHa/FSH/hCG only.The total gonadotropin(Gn)doses required,endometrial thickness,oocyte numbers,high quality embryo production rate and pregnancy rate of the two groups were compared.The concentration of growth differentiation factor-9(GDF-9)in follicular fluid was detected by western blotting and the expression of GDF-9 mRNA in granulosa cells was measured using reverse tran-scription-polymerase chain reaction amplification.RESULTS:In the experimental group,the Gn dose was significantly lower than that in the control group;the endometrial thickness,high quality embryo production and pregnancy rates were significantly higher and the expression of GDF-9 mRNA was also significantly higher than in the control group(all P<0.05).CONCLUSION:Shugan treatment can improve the pregnancy rate of women with tubal infertility;its mechanism is possibly related to the increased expression of GDF-9 in granulosa cells.

Case of acupuncture combined with Chinese herbal medication in assistance of pregnancy after 11 failures of IVF-ET at advanced age

This paper reports one case of successful pregnancy in the assistance of acupuncture therapy for regulating menstruation and promoting pregnancy and the periodic intervention with Chinese herbal medicine in a 41-year-old patient with infertility.The patient suffered from 11 failures in the assisted reproductive technique during 3 years.This case suggests that the combined treatment with acupuncture for regulating menstruation and promoting pregnancy and the periodic intervention with Chinese herbal medicine increase the levels of follicle-stimulating hormone(FSH)and estradiol(E2),improve the oocyte quality and the uterine environment.This therapeutic method plays a positive auxiliary role in the whole process of in vitro fertilization and embryo transfer(IVF-ET)and it can be adopted as an intervention for patients with multiple assisted reproductive failures.

Curative effect of assisted reproduction technology by Traditional Chinese Medicine multi-channel interventional therapy on 95 cases of in vitro fertilization and embryo transfer failure

OBJECTIVE: To evaluate the curative effect of Traditional Chinese Medicine(TCM) multi-channel interventional therapy on women with Assisted Reproductive Technology(ART) failure, to compare the curative effect of the dual therapy and triple therapy on women with ART Failure, and to choose the best TCM interventional therapeutic plan.METHODS: The 95 cases with ART Failure from West China second University Hospital of Sichuan University meeting the inclusion criteria were randomly divided into three groups:dual therapy group(31 cases), triple therapy group(33 cases)and control group(31 cases). According to the intervene treatment of in vitro Fertilization and Embryo Transfer(IVF-ET) long cycle scheme, the control group wait naturally for 3 months before IVFET. The dual therapy group take TCM prescriptionⅡ of cultivating emotion and assisting reproduction and auricular acupoint therapy for 3 months before IVF-ET, then Western Medicine treatment progestin supporting as well as auricular application and Antai Recipe after IVF-ET transplantation.The triple therapy group take TCM prescription Ⅱof cultivated emotion and assisted reproduction,auricular acupoint therapy and retention enema of TCM, and combination treatment the same as dual therapy group after transplantation. The natural pregnancy number, the period condition of secondary IVF-ET and the improvement of the kidney deficiency, liver depression and blood stasis syndrome among those three groups were compared.RESULTS: It was showed from analysis in 95 cases with ART failure that the number of natural preg-nancy was as followings: 3 patients from the dual therapy group, 10 patients from the triple therapy group, and no patient from the control group. The comparison among three groups have statistical significance(P < 0.05). The treatment group is superior to the control group, while the triple therapy is superior to the dual therapy. The comparison of the condition of the fertility rate, clinical pregnancy rate, biochemical pregnancy rate and early abortion rate during the period of secondary IVF-ET between pre-therapy and post-treatment of both the dual therapy group and the triple therapy group have statistical significance(P < 0.05). The comparison of the improvement of the kidney deficiency,liver depression and blood stasis syndrome between pre-therapy and post-treatment of both the dual therapy group and the triple therapy group have statistical significance(P < 0.05). The comparison between three groups after treatment have statistical significance(P < 0.05).CONCLUSION: TCM multi-channel interventional therapy can increase the natural pregnancy rate of patients with ART Failure(the triple therapy is superior to the dual therapy); it can increase the fertility rate, clinical pregnancy rate, and decrease the early abortion rate during the period of secondary IVF-ET; it can improve syndromes of kidney deficiency, liver depression and blood stasis.

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

An association between assisted reproductive technology （ART） and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic erros or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer （IVF-ET） on transgenerational inheritance in am inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions （DMRs） were analyzed by Morris water maze, hematoxylin and eosin （H＆E） staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF （F1） and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation （0.40±0.118, P=0.086）. Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonel stimulation and gamete manipulation might not affect the individuals and their descendents.

Effect of traditional Chinese comprehensive therapy on gestation in patients with previously failed in vitro fertilization and embryo transfer

OBJECTIVE: To explore the effect of traditional Chinese comprehensive therapy(TCCT) on promoting gestation in patients with previously failed in vitro fertilization and embryo transfer(IVF-ET) because of kidney deficiency, liver stagnation, and blood stasis(KLB).METHODS: Sixty-seven patients were enrolled in this study and divided into two groups: a trial group with 35 patients and a control group with 32 patients. The trial group was given TCCT for 3months, then administered IVF-ET or awaited natural pregnancy. The control group was administered IVF-ET without TCCT 3 months after the previous IVF-ET or natural pregnancy attempt. The patterns of KLB were observed both before and after treatment. The natural pregnancy rate of the two groups was calculated after treatment. Differences between the two groups were compared after using IVF-ET treatment again in fertilized egg number and fertilization rate were evaluated.RESULTS: After treatment with TCM comprehensive therapy, seven patients in the treatment group became pregnant, while there were no successful conceptions in the control group. The difference in clinical pregnancy rate in the initial cycle and transfer cycle of IVF were significantly different(P <0.05). The trial group had a significantly higher conception rate than that of the control group(P <0.05).CONCLUSION: TCCT can promote the natural pregnancy rate in patients with previously failed IVF-ET.TCCT could increase patients' fertilized egg number, fertilization rate, pregnancy rate, and clinical pregnancy rate after another IVF-ET treatment.TCCT can also relieve the symptoms of KLB.

Selective Short-term Fertilization Combined with Early Rescue ICSI: An Optimal Strategy for Patients at High Risk for Fertilization Failure

Objective To investigate clinical outcomes in patients who were at more precise criteria risks for fertilization failure and were treated with selective, short-term fertilization （oocytes and sperm co-incubated for 4 h） and early rescue intracytoplasmic sperm injection （ICSI）. Methods A retrospective analysis was performed on 2023 women undergoing assisted reproductive technology （ART）. They were assigned to 4 groups： short-term in vitro fertilization （short-term IVF,, group A, n=217）, regular IVF （oocytes and sperm coincubated overnight, group B, n=1475）, short-term IVF and early rescue ICSI （shortterm ICSI, group C, n=94）, and regular ICSI （group D, n=237）. Results In group A, 69.8% （217/311） achieved normal fertilization rates, and the complete fertilization failure rate （fertilization rate was 0%） was 12.9% （40/311）. But all of the fertilization failure oocytes got rescue ICSI. In group B, the complete fertilization failure rate was 1.1% （19/1 692）. The fertilization rate, 2 PN （pronucleus） rate, and i PN rate were significantly lower in group A than those in group B （70.9% vs 80.8%, 57.8% vs 66.3%, and 3.5% vs 6.2%, respectively）. No significant differences were observed in clinical pregnancy rates and birth defect rates between groups A and B. The fertilization rates in groups C and D did not significantly differ （77.9% vs 76.2%）, which was also true for birth defect rates. The clinical pregnancy rate of group C was higher than that of group D （51.2% vs 42.3%）, but this difference was not significant （P〉0. 05）.Conclusion These results suggested that selective, short-term fertilization can result in effective outcomes for patients who were at high risk for fertilization failure.