Letter to the editor“regarding case report of chronic cornual ectopic pregnancy presenting as large cornual mass after in vitro fertilization-embryo transfer”

We read the Yang et al,published case report in Laparoscopic,Endoscopic and Robotic Surgery.2019.https://doi.org/10.1016/j.lers.2019.09.001,with great interest.Yang et al,in the introduction mentioned that the cornual ectopic pregnancy is defined as a pregnancy that is abnormally located in the proximal portion of the fallopian tube,lying within the muscular wall of the uterus.

Effect of different fertilization time after human chorionic gonadotropin injection on fertilization outcome of patients in vitro fertilizationembryo transfer

Objective:To explore the effect of different fertilization time after human chorionic gonadotropin(HCG)injection on the outcome of fertilization in vitro fertilization-embryo transfer(IVF-ET).Methods:One thousand one hundred and forty IVF-ET cycles from January 2016 to August 2018 were analyzed retrospectively.According to the different fertilization time after injection of HCG divided into four groups:Group A(38.0 h~39.0 h),Group B(39.1 h~40.0 h),Group C(40.1 h~41.0 h),and Group D(41.1 h~42.0 h).The normal fertilization rate,the normal cleavage rate,the embryo utilization rate,the high-quality embryo rate,the clinical pregnancy rate,the implantation rate,and the spontaneous abortion rate were analyzed among the groups.Then we investigated the effect of different promotion methods on the outcome of fertilization during the optimal fertilization time.Results:There was no significant difference in 2PN cleavage rate,available embryo rate,clinical pregnancy rate,implantation rate and abortion rate among the four groups(P>0.05).The high-quality embryo rate in Group D(44.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate in Group D(71.6%)was the highest,and was significantly different among the four groups(P<0.05).The normal fertilization rate(78.1%)of antagonist group was significantly higher than other groups(P<0.05).Conclusion:The different fertilization time after HCG injection have effects on high-quality embryo rate and normal fertilization rate of patients in IVF-ET.The appropriate fertilization time of patients in IVF-ET was 41 h~42 h after HCG injection in our reproductive center,improved the clinical pregnancy rate and reduced the early abortion rate.The GnRH-ant protocol is superior to other protocol in IVF-ET.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve:A Prospective,Open-Labeled,Randomized and Controlled Study

Objective:To explore the effects of Zishen Yutai Pills(ZYPs)on the quality of oocytes and embryos,as well as pregnancy outcomes in patients with diminished ovarian reserve(DOR)receiving in vitro fertilizationembryo transfer(IVF-ET).The possible mechanisms,involving the regulation of bone morphogenetic protein 15(BMP15)and growth differentiation factor 9(GDF9),were also investigated.Methods:A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio.The patients in the treatment group(60 cases)received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone(Gn RH)antagonist protocol.The patients in the control group(60 cases)received the same protocol but without ZYPs.The primary outcomes were the number of oocytes retrieved and high-quality embryos.Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes.Adverse events were assessed by comparison of the incidence of ectopic pregnancy,pregnancy complications,pregnancy loss,and preterm birth.Contents of BMP15 and GDF9 in the follicle fluids(FF)were also quantified with enzymelinked immunosorbent assay.Results:Compared with the control group,the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group(both P<0.05).After treatment with ZYPs,a significant regulation of serum sex hormones was observed,including progesterone and estradiol.Both hormones were up-regulated compared with the control group(P=0.014 and 0.008),respectively.No significant differences were observed with regard to pregnancy outcomes including implantation rates,biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and pregnancy loss rates(all P>0.05).The administration of ZYPs did not increase the incidence of adverse events.The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group(both P<0.05).Conclusions:ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET,resulting in increments of oocytes and embryos,and up-regulation of BMP15 and GDF9 expressions in the FF.However,the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes(Trial reqistration No.Chi CTR2100048441).

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen(Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer

Objective: To observe the effects of electroacupuncture(EA) on reproductive outcomes in women with Shen(Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer(IVF-ET),and explore the underlying molecular mechanism.Methods: Sixty-six infertile patients with Shen de?ciency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table,33 cases in each group.Before undergoing IVF,patients in the EA and control groups received EA therapy and placebo needle puncture,respectively,for 3 menstrual cycles.Shen de?ciency syndrome scores were assessed.Other outcome measures included the number of retrieved oocytes and fertilization,high-quality embryo and clinical pregnancy rates.Follicular ?uid was collected on the day of oocyte retrieval,and granulosa cell expression of phosphatidylinositide3-kinases(PI3 K),serine-threonine kinase(Akt) and forkhead box O3(Foxo3 a) m RNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.Results: Syndrome scores for pre-versus post-treatments decreased significantly(16.53±1.75 to 8.67±1.61) in the EA group(P<0.05),but showed no signi?cant change in the control group(17.18±1.58 to 14.74±1.58).A signi?cant difference in score change was found between the EA and control groups(P<0.05).High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15%(195/282) vs.60.27%(176/292) and 66.67%(22/33) vs.42.42%(14/33),respectively,P<0.05].The fertilization rate was equivalent in EA and control groups.No difference was found in the number of retrieved oocytes between the two groups.Granulosa cell expression levels of PI3 K and Akt m RNA were signi?cantly increased in the EA group compared with the control group,while the expression of Foxo3 a was reduced(all P<0.05).Conclusions: For infertile patients with Shen de?ciency syndrome undergoing IVF,EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate.The EA-induced mechanism may involve regulation of PI3 K/Akt/Foxo3 a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis,possibly contributing to the improved clinical pregnancy rate(Registration No.Chi CTR 1800016217).

Effects of Acupuncture on Endometrium and Pregnancy Outcomes in Patients with Polycystic Ovarian Syndrome Undergoing in vitro Fertilization-Embryo Transfer:A Randomized Clinical Trial

Objective:To observe the effect of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovary syndrome(PCOS)infertility undergoing in vitro fertilization-embryo transfer(IVF-ET).Methods:Eighty-three patients were randomly assigned to observation group(40 cases)and control group(43 cases)according to the random numbers generated by SPSS software.The patients of the two groups received GnRH agonist long protocol as a routine treatment.In the observation group,acupuncture was given at two acupoint groups for 30 min once every other day.Group 1 included Guanyuan(CV 4),Qihai(CV 6),Zhongji(CV 3),bilateral acupoints Zigong(EX-CA1).Group 2 included Mingmen(GV 4),Yaoyangguan(GV 3),bilateral Shenshu(BL 23)and Ciliao(BL 32).The two groups of acupoints were used alternately.The whole needling process was performed at the time of ovulation induction until the transplantation day and consisted of3 courses,while the control group did not receive acupuncture interventions.The Gn dosage and Gn stimulation time,endometrial thickness and type(A,B,and C),serum oestradiol(E2)and progesterone(P)levels on the day of injection of human chorionic gonadotropin(hCG),clinical pregnancy rate,as well as live birth rate were observed.Adverse reactions were also be recorded.All patients were followed up for the pregnant rate 14 days after IVF-ET and live birth rate after pregnancy.All adverse reactions(AEs)of acupuncture were recorded during the trial.Ressults:The Gn dosage and Gn stimulation time in the observation group were lower in the observation group than in the control group(P<0.01).The proportion of type A endometrium in the observation group were higher than that in the control group(P<0.05).The serum E2 and P levels on the day of hCG injection was lower and the clinical pregnancy rate was higher in the observation group compared to those in the control group(P<0.05).There was no serious AEs during this trial.Conclusion:Acupuncture can improve the proportion of type A endometrium,regulate the levelse of serum Eand P on the day of hCG injection,and improve the pregnancy rate in patients with PCOS infertility undergoing IVF-ET.

Effect of Patient Age and Embryo Parameters on Pregnancy Outcomein In Vitro Fertilization-Embryo Transfer(IVF-ET)

Objective To study the effect of patient age, the number and quality of embryos transferred on pregnancy outcome in in vitro fertilization-embryo transfer procedures （IVF-ETs）. Methods A retrospective study was conducted with infertile women who underwent a total of 1 800 cycles of lVF-ET and intracytoplasmic sperm injection （ICSI） at the Reproductive Medicine Center of the Third Affiliated Hospital of Guangzhou Medical College from Jan. 2006 to Dec. 2007. The patients were divided into three groups based on age （year）. 〈30, 30-34 and 235. The rates of clinical pregnancy and multiple pregnancies were compared in each group when 1-3 embryos and 0-3 goodquality embryos were transferred respectively. Results 1） In the group of patients aged 〈30 years, there was no significant difference in pregnancy outcomes with 1-3 embryos transferred. However, pregnancy rates were similar when 2 3 good-quality embryos were transferred, which was significantly higher compared with 0-1 good-quality embryos transferred; the incidence of multiple pregnancies was not an issue when only 1 embryo was transferred. 2） The pregnancy rate of the patients aged 30 34 was not significant not only when only 2-3 embryos were transferred but also when 2-3 good-quality embryos were transferred, which was significant compared with when 1 embryo or 0 1 good-quality embryo was transferred. The subgroup of 3 good-quality embryos transferred, at the same time, was expected to significantly increase multiple pregnancy rate. 3） For the patients aged 235, there were similar pregnancy rates in the subgroup involving 1-3 embryos transferred. Compared with 0-2 good-quality embryos transferred, the pregnancy rate was significantly higher in the patients with 3 good-quality embryos transferred. An increased trend toward multiple pregnancies was observed among not only the subgroups with 1-3 embryos transferred, but also when 1-3 good-quality embryos were transferred, although it was significantly higher in patients with 3 good-quality embryo transferred. Conclusion In an effort to achieve the ideal pregnancy rate without the risk of multiple pregnancies, it is desirable to employ a single good-quality embryo transfer for patients aged 〈30 years and 2 good-quality embryos for patients aged 330. As older women （aged 335 years）, this is important, need to abstain from poor-quality embryo transferred by increasing the number of embryos transferred in an effort to improve the rate of clinical pregnancy, if the patients have had enough 2 high-quality embryos.

Analysis of Factors Influencing the Cumulative Pregnancy Outcome of In Vitro Fertilization-Embryo Transfer in Women Aged 35 Years and Older with Normal Ovarian Reserve

Background:To investigate the factors associating with the cumulative clinical pregnancy outcome of in vitro fertilization-embryo transfer(IVF-ET)in women aged 35 years and older with normal ovarian reserve.Methods:A total of 358 patients undergoing IVF-ET at the Department of Reproductive Medicine,the First Affiliated Hospital of Xinjiang Medical University between January 2014 and June 2016 were analyzed by the Kaplan-Meier method and Cox proportional hazards model.Results:The probability of pregnancy in women 35-37 years of age and 38-40 years of age was 75.9%(95%confidence interval[CI]:75.1%-76.7%)and 66.9%(95%CI:65.6%-68.2%),respectively,and it was 37.8%(95%CI:34.7%-41.1%)in women aged 40 years and older.Univariate analysis(hazard ratio[HR]:2.50,95%CI:1.647-3.774)and multivariate analysis(HR:2.17,95%CI:1.427-3.268)showed a correlation between the number of retrieved oocytes and successful pregnancy.Conclusions:The number of retrieved oocytes plays a key role in the pregnancy outcome of women aged 35 years and older with normal ovarian reserve.We recommend the number of retrieved oocytes be increased for women aged 35 years and older with normal ovarian reserve.

精子形态对体外受精－胚胎移植治疗结局的影响

目的：探讨正常形态精子百分率对体外受精-胚胎移植（IVF-ET）治疗结局的影响。方法回顾分析于生殖医学中心接受治疗的323个IVF-ET周期，采用WHO第5版精液质量分析标准严格进行精子形态学分析，研究分3组：A组：1%≤正常形态精子百分率﹤2.5%，中度畸形组；B组：2.5%≤正常形态精子百分率﹤4%，轻度畸形组；C组：正常形态精子百分率≥4%，正常形态组。比较各组间受精率、卵裂率、可移植胚胎率、优质胚胎率、着床率、临床妊娠率。结果各组间女方年龄、不孕年限、男方年龄差异均无统计学意义（P﹥0.05）。三组患者间多精受精率、双原核卵裂率、可移植胚胎率、优质胚胎率、着床率、临床妊娠率等差异均无统计学意义（P﹥0.05），但随着正常形态精子比率升高，受精率随之升高，三组之间差异有统计学意义（P﹤0.05）。结论在常规IVF-ET中，精子形态可在一定程度上影响卵子的受精率，但与胚胎质量、妊娠结局无明显相关性。

Relationship between Pronuclear Scoring and Embryo Quality and Implantation Potential in IVF-ET

To assess the relationship between pronuclear scoring and day-3 embryo quality and pregnancy outcome and to determine the Clinical value of pronuclear stage scoring system in human in vitro fertilization-embryo transfer （IVF-ET） program, a pronuclear scoring system was used to score zygotes 16-20 h after insemination during conventional IVF or intracytoplasmic sperm injection （ICSI）. The embryos were classified into groups Z1, Z2, Z3 and Z4, Comparisons were made of the rates of arrested embryos and excellent embryos on day 3. Comparisons of pregnancy outcome were made only in those patients in whom cohorts of similarly Z-scored embryos were transferred, The results showed that there were less arrested embryos and more excellent embryos on day 3 in groups Z1 and Z2 than those in group Z3 and Z4, More embryos arrested and less excellent embryos developed in group Z4 than group Z3. The clinical pregnancy rates resulting from the transfer of single pronuclear score homologous embryo types were similar among groups Z1, Z2 and Z3. Implantation rates of group Z1 were higher （P〈0.05） than that of group Z3, These findings suggests that pronuclear scoring can predict developmental ability on day 3 and implantation potential. A evaluation that combines the Z-score and day 3 embryo morphology is useful in the determination of the most viable embryos and the number of embryos for transfer.

Related Factors of in vitro Fertilization and Embryo Transfer Patients with Complete Fertilization Failure

Objective To find the possible factors predicting fertilization failure of in vitro fertilization-embryo transfer （1VF-ET）. Methods The IVF-ET patients with complete fertilization failure （experimental group, n =32） were analyzed retrospectively. The patients whose oocytes retrieved at the same day and cultured on the same incubators with ≥ 50% fertilization rates were matched as the control （n=56）. Results The infertility duration, superovulation days, the rates of primary case, progesterone （P） level 〉3.12 nmol/L rate and rate of severe abnormal sperm （abnormal sperm rate 〉95%） in experimental group were significantly higher than those in the control （6.4 ±3.1 years, 12.6 ±2.2 d, 56%, 43%, 43% vs 4.6±2.9years, 11.6 ±% 1.3 d, 33%, 23%, 23%, respectively, P〈0.05）. Conclusion We should pay attention to these patients with primary infertility, longer infertility duration and superovulation days （〉6.4 years and 〉12.6 d） and having increased level of P on hCG injection day （〉3.12 nmol/L）, abnormal sperm rate 〉95% at the same time. They should be included in such patients at high risk of fertilization failure.

Assessment of Uterine Receptivity by Endometrial and Subendometrial Blood Flows Measured by Vaginal Color Doppler Ultrasound in Women Undergoing IVF Treatment

Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infertile patients undergoing the first IVF/ICSI-ET cycle were recruited. Three groups were divided according to a color Doppler ultrasound examination performed on the day of hCG injection. Group A, endometrial and subendometrial blood flows were 2 branches and below; group B, endometrial and subendometrial blood flows were between 3 and 4 branches; group C, endometrial and subendometrial blood flows were 5 branches and above. Patients were transferred 1-3 embryos each. Demographic data, ovarian responses, endometrial thickness, PI, RI, development of embryo and IVF result among groups were compared. Results Demographic data, ovarian responses, endometrial thickness, PI, RI and development of embryo among groups have no significant difference. The pregnancy rate of group A was significantly lower than that of group B （P〈0.05） and group C （P〈0.01）. The implantation rate of group A was significantly lower than than of group C （P〈0.01）. There was no significant difference of the rate of pregnancy and implantation between group B and group C （P〉0.05）. Conclusion Endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound is a good predicator of pregnancy during IVF treatment. A good endometrial and subendometrial blood flows is benefit for the result of IVF.

Impact of Body Mass Index on In Vitro Fertilization–Embryo Transfer Outcomes in Xinjiang,China

Background:To investigate the effect of body mass index(BMI)on the outcomes of in vitro fertilization–embryo transfer(IVF-ET)treatment,and to provide evidence for future clinical studies of infertile women with different body mass indices.Methods:The relationship between pregnancy outcome and BMI in 717 infertile women who underwent IVF-ET was analyzed.Results:A total of 531 out of 717 patients were classified as having a standard body weight,and 20 patients were classified as obese.We found a significant difference in the basal follicle-stimulating hormone(FSH)level among the groups;the basal FSH level was lower in the obese group(6.80±2.20 IU/L)than in the standard weight group(7.56±2.25 IU/L).However,there were no significant differences in the age of females,the age of males,basal estradiol(E2)and luteinizing hormone(LH)levels,length of infertility,and history of dysmenorrhea.Although the pregnancy rate was highest(54.6%)in the standard weight group and lowest(45.0%)in the obese group,there was no significant difference among these groups by Chi-square test analysis.Furthermore,there were no significant differences in gonadotropin-releasing hormone agonist days,number of 2PN,and the LH level on the day of human chorionic gonadotropin treatment among the groups.Conclusions:Obese women can improve a successful pregnancy rate after undergoing IVF–ET treatment by controlling weight.

Expression of Cellular FLICE-like Inhibitory Protein in Granulosa Cells in In Vitro Fertilization Patients with Advanced Endometriosis

Background:This study evaluated the expression of cellular FLICE-like inhibitory protein(cFLIP)in granulosa cells(GCs)obtained from in vitro fertilization-embryo transfer patients with advanced endometriosis.Methods:A total of 267 patients with advanced endometriosis were enrolled in this study.They were divided into clinical pregnancy group(n=114)and nonpregnancy group(n=153).The expressions of cFLIP in mRNA and protein level were measured by real-time polymerase chain reaction(RT-PCR)and Western blotting.The related factors on the clinical pregnancy were analyzed using logistic regression analysis.Coefficients of correlation were calculated using the nonparametric rho-Spearman test.Results:The number of oocytes retrieved,fertilization rate,and cleavage rate were significantly and independently related with clinical pregnancy(P>0.05).RT-PCR and Western blotting analysis showed that the expressions of cFLP in mRNA and protein level were significantly higher in the clinical pregnancy group than in nonpregnancy group(P>0.05).cFLIP had a significantly positive correlation with the number of oocytes retrieved(P>0.05)and no correlation with fertilization rate and cleavage rate(P<0.05).Conclusion:Higher expression of cFLIP increased the pregnancy rate in women with advanced endometriosis.

基于复杂网络技术探讨针灸辅助体外受精-胚胎移植选穴规律

Objective To analyze the rules of acupoint selection in adjuvant interventions for in vitro fertilization-embryo transfer(IVF-ET)with acupuncture and moxibustion,with the use of complex network technology.Methods Articles on clinical trials of acupuncture and moxibustion for IVF-ET were searched in the China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of Science databases from inception to January 31,2020.A database of acupoint prescriptions has been established.Descriptive analysis was conducted using Microsoft Excel 2019,association rule analysis was conducted using SPSS Modeler 18.0 Apriori algorithm,clustering analysis of high-frequency acupoints was performed using SPSS 25.0 Ward,and complex network analysis of acupoints was performed by using Gephi 0.9.2.Results A total of 124 clinical trials were included,and 187 acupoint prescriptions were extracted,for a total of 91 acupoints.The total frequency of using these acupoints was 1,296 times,with Sānyīnjiāo(三阴交SP6)used the most frequently.The acupoints were generally located around the conception vessel,spleen meridian,and stomach meridian,and they were mainly distributed in the lower extremities,chest,and abdomen.Considerable consideration was paid to the specific points.The association rule analysis showed that the highest correlation presented between Guānyuán(关元CV4)and Zĭgōng(子宫EX-CA1).Complex network k-core hierarchical analysis discovered that CV4,SP6,Xuèhăi(血海SP10),Hégŭ(合谷LI4),Tàichōng(太冲LR3),Qìhăi(气海CV6),and EX-CA1 were the core acupoints in adjuvant interventions with acupuncture-moxibustion for IVF-ET.Conclusion In adjuvant interventions with acupuncture-moxibustion,acupoints were commonly located around the conception vessel,spleen meridian,and stomach meridian,and the convergent point was particularly used as a specific point.The acupoints were selected to smooth the liver qi,remove stagnation,activate blood circulation,resolve stasis,and benefit the liver and kidney.“CV4→SP6→EX-CA1→ST36”were the core points,and CV4 was the core prescription in adjuvant treatments with acupuncture-moxibustion in IVF-ET.

Expectant management of heterotopic cesarean scar pregnancy

Background Heterotopic cesarean scar pregnancy （HCSP） is a very rare but life-threatening entity and there is no optimal management strategy. Here we report a successfully managed case of HCSP with expectant treatment in a tertiary referral hospital. Methods A woman with HCSP after in vitro fertilization-embryo transfer opted for expectant treatment after five days of mild bleeding and ultrasound demonstrated cardiac activity disappearance of the scar pregnancy at 8＋4 weeks of gestation. Results The patient had mild to moderate bleeding during close monitoring. Three days later, speculum examination revealed the gestational mass was partly protruding at the os of the cervix and it was removed with forceps without massive hemorrhage. A healthy male baby was delivered by cesarean section at gestational age of 36＋4 weeks. Conclusions The expectant method might be an alternative option for a HCSP with loss of cardiac activity of the scar pregnancy, when applied under supportive management and with available emergency surgery facilities.

Clinical Analysis on IVF-ET Treatment of 9 Cases of Post-cesarean Section Uterine Diverticulum

Objective To evaluate the influence of uterine diverticulum patients who have a history of cesarean section on IVF-ET process and pregnancy outcome. Methods Nine patients with uterine diverticulum after cesarean were retrospectively analyzed, who have received IVF-ET treatment. Clinical pregnancy rate and embryo implantation rate were measured. Results There were 9 infertility patients in all, 7 cases with tubal factor, 2 with unexplained factor; 3 cases were associated with prolonged menstruation period, including 1 patient was misdiagnosed as dysfunctioned uterine bleeding. There were a total of 16 transplantation cycles, including14 fresh cycles and 2 thawing cycles. Each cycle had at least one high-quality embryo available for transfer. Five cases were difficult to transfer. Two were clinical pregnancie, the implantation rate was 5.13% （2/39）. Conclusion In this study, 14 fresh cycles all had high-quality embryo transfer, uterine diverticulum had no effect on the development of ovums and the formation of high- quality embryos. But forming uterine diverticulum after cesarean section may lead to secondary infertility or patients with prolonged menstruation period, it also may lead it difficult to transfer during the treatment of IVF-ET and affect embryo implantation. So the patients with a history of cesarean section shall receive ultrasonic examination or hysteroscopy routinely before IVF treatment. If necessary surgical treatment is required.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Trial

Objective:To evalvate efficacy of Qizi Yusi Pills(QYP),a Chinese medicine compound preparation,on in vitro fertilization-embryo transfer(IVF-ET)in women of advanced reproductive age.Methods:This multicenter,randomized,double-blind,placebo-controlled trial was conducted from June 2018 to October2019.A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design,with 62 patients in each group.All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist(GnRH-a)long protocol.As the QYP group,QYP was administered while the control group received placebo.QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval.Both medications were taken orally at doses of 10 g three times each day.The primary outcome was cumulative pregnancy rate,and the secondary outcomes were periodic medication,follicular status,serum hormone and endometrial receptivity.Follow-up continued until 4 weeks after delivery.Maternal and neonatal complications,such as gestational diabetes,were also observed.Results:Overall,119 patients completed the study,60 in the QYP group and 59 in the placebo group.Per protocol(PP)analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group[43.33%(26/60)vs.25.42%(15/59),P=0.040].Additionally,more oocytes were retrieved from the QYP group than those from the placebo group(8.95±3.12 vs.7.85±1.91,P=0.022).Moreover,the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group(11.78±2.27 mm vs.10.68±2.07 mm,P=0.012).Maternal and neonatal complications between the two groups were not significantly different(P>0.05).Intention-to-treat analysis was in line with PP results.Conclusions:QYP can enhance ovarian reserve capacity and ovarian response,and possibly promote endometrial receptivity.QYP effectively improves cumulative pregnancy rates in older patients(≥35 years)undergoing IVF-ET.(Registration No.ChiCTR1800014427).

Effect of Uterine Anomalies on Pregnancy Rates and Reproductive Outcomes in Women Undergoing Artificial Insemination by Husband

Objective: Congenital uterine anomalies are common; however, their effects on artificial insemination by husband(AIH) and the period during which AIH is converted to in vitro fertilization(IVF) are unclear. We examined the influence of uterine malformations on reproductive outcomes following AIH and the optimum number of AIH cycles before resorting to IVF-embryo transfer(IVF-ET).Methods: We retrospectively recruited 168 patients with uterine malformations(anomalous group) undergoing AIH between January 2011 and December 2016. Meanwhile, 168 patients with infertility but with normal uteri(normal group) were matched as controls according to age.Results: The clinical pregnancy rate was similar in both groups(12.4% vs. 12.3%, P=0.950); the cancellation(21.6% vs. 4.4%, P< 0.001),early pregnancy loss(35.7% vs. 11.4%, P = 0.032), and preterm birth rates(21.4% vs. 2.9%, P = 0.038) were higher in the anomalous group,resulting in lower term birth(32.1 % vs. 74.3%, P =0.001) and live birth rates(50.0% vs. 77.1 %, P = 0.034). After two AIH cycles, the clinical pregnancy rate was lower(3.6% vs. 23.1%, P = 0.037) among women with uterine anomalies than among those with normal uteri. There was no difference in the pregnancy rates(52.5% vs. 53.7%, P= 0.908) between the two groups of patients with unsuccessful AIH who then underwent IVF-ET.Conclusions: IVF-ET can be performed immediately after two unsuccessful AIH cycles in patients with uterine malformations. In patients undergoing AIH or IVF, uterine malformations increase the risk of adverse obstetric outcomes.

Effects of Triggering Oocytes Maturation by rhCG 250 μg vs uhCG 10 000 IU on the Outcomes of IVF-ET Treatment in Chinese Population:A Cohort Study

Objective To compare the effects of recombinant hCG （rhCG） 250 μg and urinary hCG （uhCG） 10 000 1U on triggering oocyte maturation during COH/1VF-ET in Chinese women. Methods A retrospective cohort study which included COH/1VF-ET cases at reproductive medical center of Peking University Third Hospital from March to May 2010 was performed. Analysis of covariance （ANCOVA） was taken for data analysis. Results There were 318 cycles （group A） using rhCG 250μg and 810 cycles （group B） using uhCG 10 000 1U for triggering. In 1VF procedure, there were no significant differences in the number of oocyte retrieval, 2PN fertilization rate, good-quality embryo rate, embryo implantation rate and clinical pregnancy rate between the two groups. The delivery weeks, mean neonatal birth weight and live birth rates were also similar between the two groups. There was no local allergic reaction after injection or neonatal birth defect in group A. Conclusion The rhCG 250 μg and uhCG 10 000 IU have equal effects on triggering oocyte maturation for patients with normal ovarian function in Chinese population. rhCG may have even lower local discomfort occurrence.

Different Pretreatments before Application of GnRH Antagonist Protocol in Controlled Ovarian Hyperstimulation

Objective To analyze the clinical features and outcome of patients who used different pretreatments before application of gonadotropin-releasing hormone antagonist protocol during in vitro fertilization - embryo transfer （IVF-ET） cycles, and to explore how effective to use the antagonist protocol. Methods A retrospective analysis was performed. All the ET cycles were divided into three groups, group A （n=125） used short acting GnRH agonist before GnRH antagonist treatment, group B （n=113） used short-acting oral contraceptives before GnRH antagonist treatment, group C （n=81） was untreated before GnRH antagonist treatment. All the patients had no tubal fluid, endometrial polyps and no anatomical abnormalities of the uterus, from April 2010 to December 2010. The patient＇s age, dose and duration of gonadotropin （Gn） treatment, the serum LH and E2 levels on the day of hCG injection, the number of oocytes retrieved, the rates of good-quality embryos, the clinical pregnancy rates were compared. At the same time, 261 GnRH agonist long protocol cycles （group D） were selected at the same period as further comparison. Results The patients in group C （32.9 ~ 4.8 years） were significantly older than those in groups A and B （31.6 ___＋3.7 years, 31.2 ___%4.1 years）（P 〈0.05）. The dose and the duration of Gn in group C were significantly lower than those in groups A and B. The serum LH level on the day of hCG injection in group A and group B was significantly lower than that in group C （P 〈0.05）, especially in group A. The endometrium was the thinnest in group B. There were no significant differences in the fertilization rates and the good-quality embryosrates among them. The clinical pregnancy rate of group B decreased significantly compared with groups A and C （P〈0. 05）. The clinical pregnancy rate of group C was the highest among them. There was no significant difference of clinical pregnancy rates between group C and group D （37% vs 40.2%,P〉0.05）. However, the dose （19.8 ±6.6 ampoule vs 26.4 ±8.1 ampoule） and the duration （9.0± 1.6 d vs 11.6±2.5 d） of Gn treatment in group C were decreased significantly than those in group D, P〈0.05. Conclusion The short acting GnRH agonist used before GnRH antagonist treatment during IVF-ET cycles failed to improve the pregnancy rates, the use of short-acting oral contraceptives before GnRH antagonist treatment makes the pregnancy rates decrease significantly, but untreated before GnRH antagonist protocol can get a better clinical outcome compared with agonist long protocol Untreated GnRH anagonist protocol is the best GnRH anagonist protocol.