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 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.

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.

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.

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。

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.

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.

Impact of Blood Clot in Oocyte-Corona-Cumulus Complex during in vitro Fertilization and Embryo Transfer

Objective To study the impact of blood clots in the oocyte-corona-cumulus complexes （OCCC） during in vitro fertilization and embryo transfer （IVF-ET）.Methods The OCCCs were harvested from the patients undergoing long protocol ovarian hyperstimulation. The OCCCs with blood clots removed or not, were randomly grouped into A or B. The OCCCs without blood clots were group C （the control）.Results The patient＇s age, infertility duration, the average GN consumption, the average days of superovulation and an average number of harvested oocytes showed no significant difference in the 3 groups. The fertilization rate and 2PN rate in group A were the highest, which were 85.4% and 71.1%, respectively, followed by group C, which were 77.5% and 64.9%, respectively. The lowest fertilization rate and 2PN rate were in group B, 75.8% and 62.2%, respectively. Those in group A were significantly higher than those in groups B and C （P〈0.01）, while there was no significant difference between group B and group C. The implantation rates and pregnancy rates showed no significant difference in the 3 groups after transplantation, even if group A got the highest rate among the 3 groups. Conclusion Removing the blood clots in OCCC can improve the outcome of IVF-ET without increasing the cost and complexity of the operation.

Is there A Link between Serum Thyroid Stimulating Hormone Level and the Results of in vitro Fertilization and Embryo Transfer?

Objective To analyze the clinical features and outcomes in infertile patients with different levels of thyroid stimulating hormone （TSH） undergoing IVF/ICSL and to investigate whether inappropriate level of TSH has the adverse effect on the results of the IVF-ET.Methods A total of 389 patients undergoing IVF/ICSI from January 2009 to December 2011 were divided into 3 groups according to the basal TSH level： group A （TSH〈 2.0 mlU/L）, group B （TSH 2.0-4.5 mlU/L） and group C （TSH〉4.5 mlU/L）. Oocyte retrieved, fertilization rate, cleavage rate, available embryo rate, pregnancy rate and miscarriage rate were analyzed to explore whether serum TSH level was correlated with the results of lVF/ICSI.Results There were no differences in number of oocyte retrieved, fertilization rate, cleavage rate and available embryo rate among 3 groups （P〉0.05）. Clinical pregnancy rate in group B （43.0%） was significantly higher than that in group A （30.2%） and group B （23.5%）, respectively （P〈0.05）. There were no significant differences in miscarriage rate among 3 groups.Conclusion TSH level has no effect on fertility rate or miscarriage rate in patients undergoing IVF/ICSL Inadequacy TSH level would decrease the IVF/ICSI pregnancy rate.

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.

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.

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.

Predictive Value of Serum Vascular Endothelial Growth Factor and Pigment Epithelium-derived Factor in Ovarian Hyperstimulation Syndrome

Objective To explore whether the serum concentrations of vascular endothelial growth factor （VEGF） and pigment epithelium-derived factor （PEDF） could serve as the predictors of ovarian hyperstimulation syndrome （OHSS） in patients undergoing in vitro fertilization-embryo transfer （IVF-ET）. Methods Enzyme-linked immunoadsordent assay （ELISA） was employed to measure the serum concentrations of VEGF and PEDF on the day of hCG administration, oocyte retrieval and embryo transfer, respectively. Based on OHSS classification of the criteria of Golan, 85 patients were divided into three groups. Patients in group A （n=10） showed symptoms of severe OHSS and patients in group B （n=13） suffered from moderate OHSS. The control group （group C, n=62） contained patients without symptoms of OHSS as well as patients with mild OHSS.Results In groups A, B and C, serum concentrations of PEDF on the day of hCG administration （h-PEDF）（166.54 ± 102.81 pg/ml, 159.45 ±136. 77 pg/ml, 172.05±170.95 pg/ml, P=0.48）, oocyte retrieval （o-PEDF）（176.91 ± 103.37 pg/ml, 122.52± 92.54 pg/ml, 179.82±177.47 pg/ml, P=0.27） and embryo transfer （e-PEDF）（169.02± 240.08 pg/ml, 136.80 ±139.21pg/ml, 157.38 ±222.54 pg/ml, P=0.95）, h-VEGF （175.55 ± 103.54 pg/ml, 218.84 ±179.70pg/ml, 153.39±145.06 pg/ml, P=0.36） and o- VEGF （171.93 ± 128.55 pg/ml, 220.36±149.82 pg/ml, 138. 74 ±% 139.30 pg/ml, P=0. 15） showed no significant differences. There was a statistical difference in serum concentration of e-VEGF between group A （197.04±156.63 pg/ml） and group C （110.69±49.55 pg/ml）（P=0.008）. The serum level of estradiol showed a positive correlation with the count of large follicles （r=0. 744）. The ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF were calculated and showed a clear difference among groups A, B and C （4.04±3.39, 2.10±2.14, 1.05± 4.80, P〈0.001; 4.54 5.69, 2.29 ±1.67, 0.94 ±0.59, P〈0.001; 5.43±6.16, 1.81±1.36, 2.42±2.60, P=0.04）. Conclusion While neither serum concentrations of VEGF nor PEDF can be used as an OHSS predictor, the ratios of h-VEGF/h-PEDF, o-VEGF/o-PEDF and e-VEGF/e-PEDF may have great predictive value.

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.

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.