Live births from in vitro fertilization-embryo transfer following the administration of gonadotropin-releasing hormone agonist without gonadotropins:Two case reports

BACKGROUND The prevalence of female infertility between the ages of 25 and 44 is 3.5%to 16.7%in developed countries and 6.9%to 9.3%in developing countries.This means that infertility affects one in six couples and is recognized by the World Health Organization as the fifth most serious global disability.The International Committee for Monitoring Assisted Reproductive Technology reported that the global total of babies born as a result of assisted reproductive technology procedures and other advanced fertility treatments is more than 8 million.Advancements in controlled ovarian hyperstimulation procedures led to crucial accomplishments in human fertility treatments.The European Society for Human Reproduction and Embryology guideline on ovarian stimulation gave us valuable evidence-based recommendations to optimize ovarian stimulation in assisted reproductive technology.Conventional ovarian stimulation protocols for in vitro fertilization(IVF)–embryo transfer are based upon the administration of gonadotropins combined with gonadotropin-releasing hormone(GnRH)analogues,either GnRH agonists(GnRHa)or antagonists.The development of ovarian cysts requires the combination of GnRHa and gonadotropins for controlled ovarian hyperstimulation.However,in rare cases patients may develop an ovarian hyper response after administration of GnRHa alone.CASE SUMMARY Here,two case studies were conducted.In the first case,a 33-year-old female diagnosed with polycystic ovary syndrome presented for her first IVF cycle at our reproductive center.Fourteen days after triptorelin acetate was administrated(day 18 of her menstrual cycle),bilateral ovaries presented polycystic manifestations.The patient was given 5000 IU of human chorionic gonadotropin.Twenty-two oocytes were obtained,and eight embryos formed.Two blastospheres were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.In the second case,a 37-year-old woman presented to the reproductive center for her first donor IVF cycle.Fourteen days after GnRHa administration,the transvaginal ultrasound revealed six follicles measuring 17-26 mm in the bilateral ovaries.The patient was given 10000 IU of human chorionic gonadotropin.Three oocytes were obtained,and three embryos formed.Two high-grade embryos were transferred in the frozen-thawed embryo transfer cycle,and the patient was impregnated.CONCLUSION These two special cases provide valuable knowledge through our experience.We hypothesize that oocyte retrieval can be an alternative to cycle cancellation in these conditions.Considering the high progesterone level in most cases of this situation,we advocate freezing embryos after oocyte retrieval rather than fresh embryo transfer.

Cumulative Live Birth Rate after Three Ovarian Stimulation IVF Cycles for Poor Ovarian Responders According to the Bologna Criteria

Summary： This study explored the cumulative live birth rate after three ovarian stimulation in vitro fer- tilization （IVF） cycles for poor ovarian responders according to the Bologna criteria. In this retrospec- tive cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cu- mulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%--24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and 〉40 years, re- spectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth, rate after three ovarian stimulation IVF cycles, especially poor responders aged 〈40 years.

Does Lower Dose of Long-acting Triptorelin Maintain Pituitary Suppression and Produce Good Live Birth Rate in Long Down-regulation Protocol for In-vitro Fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone（Gn RH） agonist in Gn RH agonist long protocol for in vitro fertilization（IVF）/intracytoplasmic sperm injection（ICSI） were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with Gn RH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group（41.2% vs. 43.7%）. The mean luteinizing hormone（LH） level on follicle-stimulating hormone（FSH） starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin（h CG） administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group（12.90±5.82 vs. 13.52±6.97）. There was no significant difference in clinical pregnancy rate between the two groups（50.5% vs. 54.5%）. It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

Successful live birth following hysteroscopic adhesiolysis under laparoscopic observation for Asherman’s syndrome: A case report

BACKGROUND Asherman’s syndrome is characterized by reduced menstrual volume and adhesions within the uterine cavity and cervix,resulting in inability to carry a pregnancy to term,placental malformation,or infertility.We present the case of a 40-year-old woman diagnosed with Asherman’s syndrome who successfully gave birth to a live full-term neonate after hysteroscopic adhesiolysis under laparoscopic observation,intrauterine device insertion,and Kaufmann therapy.CASE SUMMARY A 40-year-old woman(Gravida 3,Para 0)arrived at our hospital for specialist care to carry her pregnancy to term.She had previously undergone six sessions of dilation and curettage owing to a hydatidiform mole and persistent trophoblastic disease,followed by chemotherapy.She subsequently became pregnant twice,but both pregnancies resulted in spontaneous miscarriages during the first trimester.Her menstrual periods were very light and of short duration.Hysteroscopic adhesiolysis with concurrent laparoscopy was performed,and Asherman’s syndrome was diagnosed.The uterine adhesions covered the area from the internal cervical os to the uterine fundus.Postoperative Kaufmann therapy was administered,and endometrial regeneration was confirmed using hysteroscopy.She became pregnant 9 mo postoperatively and delivered through elective cesarean section at 37 wk of gestation.The postpartum course was uneventful,and she was discharged on postoperative day 7.CONCLUSION Hysteroscopic adhesiolysis with concurrent laparoscopy enables identification and resection of the affected area and safe and accurate surgery,without complications.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve

Objective It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization(IVF)in high or normal ovarian responders.However,it is not clear whether dual triggering also benefits patients with diminished ovarian reserve(DOR).The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone(GnRH)agonist combined with human chorionic gonadotropin(hCG)for final follicular maturation improves the cumulative live birth rate(CLBR)during the GnRH-antagonist cycle in patients with DOR.Methods This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection(IVF-ICSI)cycles at Peking University People’s Hospital from January 1,2017 through December 31,2017.Oocyte maturation was triggered by GnRH combined with hCG(n=110)or hCG alone(n=71).Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle.Patients were followed up for 3 years.Results The dual trigger treatment did not affect CLBR,which is an overall determinant of the success rate of assisted reproductive technology(ART).Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group(90.1%vs.83.9%,P=0.040).Conclusion Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR,but did slightly improve fertilization rate,oocyte count,and embryo quality.

Cumulative live birth rates of in vitro fertilization/intracytoplasmic sperm injection after multiple complete cycles in China

There were few studies of cumulative live birth rates(CLBRs) based on multicenter reproductive clinical data from the general Chinese population.Here we report a retrospective cohort study,including 14 311 women with17 315 cycles,in three reproductive centers to evaluate two estimated parameters of CLBRs with multiple transfer cycles of in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) in a Chinese population.We found that CLBRs were related to female age and endometrial thickness.By the fourth transfer cycle,the conservative and optimal estimates of CLBRs were 52.95% and 77.30% in women under 30 years of age,and 18.17% and26.51% in those 37 years of age or older,respectively.The two estimates were 44.70% and 63.15% in women with endometrial thickness more than 7 mm,and 32.05% and 46.18% in those with less than 7 mm,respectively.In addition,body mass index(BMI),duration of infertility,and infertility diagnoses may also be related to CLBRs on certain conditions.The findings from this study on CLBRs after multiple transfer cycles of IVF/ICSI treatment on different conditions in the Chinese population should be beneficial to both infertile couples and clinicians.

Predicting a live birth by artificial intelligence incorporating both the blastocyst image and conventional embryo evaluation parameters

BACKGROUND The achievement of live birth is the goal of assisted reproductive technology in reproductive medicine.When the selected blastocyst is transferred to the uterus,the degree of implantation of the blastocyst is evaluated by microscopic inspection,and the result is only about 30%-40%,and the method of predicting live birth from the blastocyst image is unknown.Live births correlate with several clinical conventional embryo evaluation parameters(CEE),such as maternal age.Therefore,it is necessary to develop artificial intelligence(AI)that combines blastocyst images and CEE to predict live births.AIM To develop an AI classifier for blastocyst images and CEE to predict the probability of achieving a live birth.METHODS A total of 5691 images of blastocysts on the fifth day after oocyte retrieval obtained from consecutive patients from January 2009 to April 2017 with fully deidentified data were retrospectively enrolled with explanations to patients and a website containing additional information with an opt-out option.We have developed a system in which the original architecture of the deep learning neural network is used to predict the probability of live birth from a blastocyst image and CEE.RESULTS The live birth rate was 0.387(=1587/4104 cases).The number of independent clinical information for predicting live birth is 10,which significantly avoids multicollinearity.A single AI classifier is composed of ten layers of convolutional neural networks,and each elementwise layer of ten factors is developed and obtained with 42792 as the number of training data points and 0.001 as the L2 regularization value.The accuracy,sensitivity,specificity,negative predictive value,positive predictive value,Youden J index,and area under the curve values for predicting live birth are 0.743,0.638,0.789,0.831,0.573,0.427,and 0.740,respectively.The optimal cut-off point of the receiver operator characteristic curve is 0.207.CONCLUSION AI classifiers have the potential of predicting live births that humans cannot predict.Artificial intelligence may make progress in assisted reproductive technology.

Improvement of Live Birth Rate Following Frozen-Thawed Blastocyst Transfer by Combination of Prednisolone Administration and Stimulation of Endometrium Embryo Transfer

The endometrial condition is a significant factor for successful pregnancy. To regulate endometrial function in fertility treatment, prednisolone (PSL) is administered for suppression of increased natural killer cells and stimulation of endometrium embryo transfer (SEET) to enhance communication between embryo and maternal tissues. We attempted to improve the endometrial condition by PSL administration and SEET during frozen–thawed blastocyst transfer (FBT). Patients took PSL (5 mg) 3 times daily for 3 days after ovulation during the FBT cycle. To analyse effects of PSL combined with SEET, we determined rates of chemical pregnancy, clinical pregnancy, foetal heart movement (FHM) and live birth. Rates of chemical pregnancy, clinical pregnancy and FHM were significantly higher in the PSL(+)/SEET(+) (57.7%, 50.0% and 46.2%, respectively) and PSL(+)/SEET(-) (53.3%, 46.7% and 46.7%, respectively) groups than in the PSL(-)/SEET(+) (30.3%, 18.2% and 18.2%, respectively) and PSL(-)/SEET(-) (22.4%, 22.4% and 18.4%;P = 0.0043, 0.0081 and 0.0055, respectively) groups. The live birth rate was significantly higher in the PSL(+)/SEET(+) group than in the PSL(+)/SEET(-), PSL(-)/SEET(+) and PSL(-)/SEET(-) groups (42.3%, 26.7%, 18.2% and 12.2%, respectively;P = 0.0237). PSL combined with SEET may be a useful adjunct to assisted reproductive technology in women who repeatedly fail to conceive by infertility treatment.

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China

Background:More and more scholars have called for the cumulative live birth rate(CLBR)of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology.This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.Methods:Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection(IVF/ICSI)cycles performed between January 2013 to December 2014.A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included.The study was followed up for 4 years to observe the CLBR.The multivariable logistic regression model was used to analyze the prognosis factor,P value of<0.05 was considered statistically significant.Results:The cumulative pregnancy rate was 58.14%(10,452/17,978),and the CLBR was 49.66%(8928/17,978).The female age was younger in the live birth group when compared with the non-live birth group(30.81±4.05 vs.33.09±5.13,P<0.001).The average duration of infertility was shorter than the non-live birth cohort(4.22±3.11 vs.5.06±4.08,P<0.001).The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group(both P<0.001).Meanwhile,the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group(15.35±7.98 vs.11.35±7.60,P<0.001;6.66±5.19 vs.3.62±3.51,P<0.001,respectively).Conclusions:The women's age,body mass index,duration of infertility years,infertility factors,controlled ovarian hyperstimulation protocol,the number of acquired oocytes,and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.

Magnetic-activated cell sorting of nonapoptotic spermatozoa with a high DNA fragmentation index improves the live birth rate and decreases transfer cycles of IVF/ICSI

The present study aimed to evaluate the clinical outcomes of magnetic-activated cell sorting(MACS)in sperm preparation for male subjects with a sperm DNA fragmentation index(DFI)≥30%.A total of 86 patients who had undergone their first long-term long protocol were selected.The protocol involved in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI)cycles,and the patients were divided into the MACS or control groups.The MACS group included sperm samples analyzed with MACS that were combined with density gradient centrifugation(DGC)and the swim-up(SU)technique(n=39),and the control group included sperm samples prepared using standard techniques(DGC and SU;n=41).No differences were noted with regard to basic clinical characteristics,number of oocytes retrieved,normal fertilization rate,cleavage rate,or transplantable embryo rate between the two groups in IVF/ICSI.In addition,the clinical pregnancy and implantation rates of the first embryo transfer cycles indicated no significant differences between the two groups.However,there was a tendency to improve the live birth rate(LBR)of the first embryo transfer cycle(63.2%vs 53.9%)and the cumulative LBR(79.5%vs 70.7%)in the MACS group compared with the control group.Moreover,the number of transferred embryos(mean±standard deviation[s.d.]:1.7±0.7 vs 2.3±1.6)and the transfer number of each retrieved cycle(mean±s.d.:1.2±0.5 vs 1.6±0.8)were significantly lower in the MACS group than those in the control group.Thus,the selection of nonapoptotic spermatozoa by MACS for higher sperm DFI could improve assisted reproductive clinical outcomes.

Prediction of Cumulative Live Birth Rate in Women Aged 40 Years and Over Undergoing In vitro Fertilization/Intracytoplasmic Sperm Injection

Objective:To investigate cumulative live birth rate (cLBR) per oocyte retrieval in infertile patients aged 40 years and over undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles and to identify the possible predictors.Methods:A total of 1,613 patients at a university hospital in China from January 2013 to May 2017 were enrolled in this retrospective study.All data for fresh and subsequent frozen-thawed cycles were analyzed.Multivariate logistic regression analysis with stepwise selection of possible predictors for cLBR was performed,and Loess curve was constructed to determine the association between cLBR and the number of oocytes retrieved.Results:cLBR significantly increased with the number of oocytes retrieved and reached up to 75% when > 20 oocytes were retrieved (P<0.001).Variables of antral follicle count (AFC) and the number of oocytes retrieved were selected using multiple logistic regression analysis with stepwise selection to predict the significance of cLBR.cLBR demonstrated an obvious upward trend as the number of oocytes retrieval increased in the Loess curve.Conclusions:For patients aged 40 years and over,AFC and the number of oocytes retrieved were two key predictors for cLBR and maximization of ovarian reserve exploitation was pivotal to increase the chance of live birth.

Use of a male antioxidant nutraceutical is associated with superior live birth rates during IVF treatment

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage.Since sperm DNA damage may reduce embryo quality and increase miscarriage rates,it is possible that untreated sperm oxidative stress may impair in vitro fertilization(IVF)live birth rates.Given that the antioxidant Menevit is reported to reduce sperm DNA damage,it was hypothesized that men’s consumption of this supplement may alter IVF outcomes.Therefore,a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer.Men were classified as controls if they were taking no supplements,health conscious controls if taking“general health”supplements,or Menevit users.Men with karyotype abnormalities,or cycles using donated,frozen and surgically extracted sperm were excluded.Among the final study cohort of 657 men,live birth rates were significantly higher in Menevit users than controls(multivariate adjusted odds ratio[OR]:1.57,95%confidence interval[Cl]:1.01-2.45,P=0.046),but not between controls taking no supplements and those using general health supplements,thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users.Interestingly,in a post hoc sensitivity analysis,live birth rates among Menevit users were statistically superior to controls for lean men(OR:2.73,95%Cl:1.18-6.28;P=0.019),not their overweight/obese counterparts(OR:1.29,95%Cl:0.75-2.22,P=0.37).The results of this large cohort study therefore support a positive association between men’s use of the Menevit antioxidant during IVF treatment and live birth rates,especially in lean individuals.

Development and Validation of a Nomogram for Predicting the Probability of Live Birth in Infertile Women

Objective:To develop a nomogram to predict the probability of live birth on the basis of the association of patient characteristics in subfertile individuals or couples.Methods:A retrospective study was conducted from January 2014 to December 2015.A nomogram was built from a training cohort and tested on an independent validation cohort.A total of 2,257 patients who had undergone their first nondonor cycle of in vitro fertilization(IVF)(including intracytoplasmic sperm injection)were randomly split 2:1 into training(n=1,527)and validation(n=730)cohorts.Results:There were no statistically significant differences in the patients’baseline and cycle characteristics between the training and validation cohorts.On multiple logistic regression analysis,female age,antral follicle count,tubal factor,anovulation,ethnicity,unexplained fertility,and male factor were significantly associated with live birth.The nomogram had a C-index of 0.700(95%confidence interval[CI]:0.698-0.701)in the training cohort and 0.684(95%CI:0.681-0.687)in the validation cohort.Conclusions:Our nomogram can predict the probability of live birth for infertile women and can be used to guide clinicians and couples to decide on an IVF treatment option.

不同治疗方案对卵巢储备功能正常年轻女性夫精人工授精妊娠结局的影响

目的探讨不同治疗方案对年龄<35岁卵巢储备功能正常女性夫精人工授精(AIH)妊娠结局的影响。方法回顾性分析2015年1月至2021年8月在本中心行AIH助孕的年龄<35岁卵巢储备功能正常女性的3024个周期的临床资料。根据治疗方案分为6组:自然周期组(NC组,n=380)、克罗米芬组(CC组,n=57)、CC联合促性腺激素(Gn)组(CC+Gn组,n=78)、Gn组(n=1712)、来曲唑组(LE组,n=430)以及LE联合Gn(LE+Gn组,n=367),比较各组患者的一般情况和妊娠结局,并采用多因素Logistic回归分析影响AIH临床妊娠率及活产率的相关因素。结果一般情况比较:6组间体质量指数(BMI)、窦卵泡数(AFC)、基础卵泡刺激素(FSH)水平、优势卵泡数、不孕因素整体比较有统计学差异(P<0.05),而女方年龄、不孕年限、不孕类型及精液处理方式比较均无统计学差异(P>0.05)。妊娠结局比较:6组患者间临床妊娠率和活产率整体比较有统计学差异(P<0.05),其中LE+Gn组的临床妊娠率和活产率显著高于NC组(分别为20.7%vs.9.5%;16.3%vs.7.4%)(P<0.05);6组间流产率、异位妊娠率及多胎率比较无统计学差异(P>0.05)。多因素Logistic回归分析结果显示,矫正混杂因素后,LE+Gn治疗方案和优势卵泡数均是临床妊娠和活产的保护因素(OR>1,P<0.05),而不孕年限是临床妊娠和活产的危险因素(OR<1,P<0.05)。结论LE联合Gn方案可显著提高AIH的临床妊娠率和活产率,可作为年龄<35岁卵巢储备功能正常女性AIH助孕的首选治疗方案。

卵巢功能减退患者多周期累积与非累积胚胎移植临床结局比较

目的探讨卵巢功能减退(DOR)患者多周期累积与非累积胚胎移植体外受精-胚胎移植(IVF-ET)临床结局的差异。方法回顾性分析2019-01至2022-12于首都医科大学附属北京妇产医院生殖医学科进行IVF-ET治疗的卵巢储备功能减退的不孕患者174例的临床资料,纳入患者均已完成所有胚胎移植及最终随访。收集患者的基础内分泌、抗苗勒管激素水平及窦卵泡计数,记录促排卵治疗后的卵巢反应参数及妊娠结局等相关临床资料,比较多周期累积胚胎移植(累积组)与非累积胚胎移植(非累积组)两种IVF-ET治疗的临床结局。结果DOR患者多周期累积胚胎移植与非累积胚胎移植两组间的累积妊娠率(35.24%vs.27.54%)、早期流产率(32.43%vs.26.32%)及累积活产率(21.90%vs.18.84%)差异无统计学意义(P>0.05);纳入移植策略、BMI、首次取卵年龄、AMH、胚胎移植数、优质胚胎移植数、累积获卵数等多个因素后进行logistic回归分析,两种不同的胚胎移植策略(OR=1.522,95%CI 0.608~3.814)对活产无明显影响(P>0.05)。结论对于DOR患者,进行多周期重复取卵后的累积胚胎移植并不能提高患者的累积妊娠率及活产率。

构建不明原因不孕症患者优质囊胚形成的临床预测模型列线图及验证

背景:不明原因不孕具有较高的流产率与较低的受精率、种植率、临床妊娠率及累积活产率。临床亟待建立不明原因不孕相关临床预测模型,以解决临床预后与开展个体化医疗服务问题,并最终达到提高不明原因不孕患者累积活产率的目的。目的:构建不明原因不孕患者在体外受精过程中优质囊胚形成与否的预测模型列线图及验证。方法:回顾性分析2017年3月至2022年6月于常州妇幼保健院辅助生殖科进行体外受精的不明原因不孕患者共419例,以其中317例形成优质囊胚患者与102例未形成优质囊胚患者建立预测模型并作为模型组,通过对模型组Bootstrap法重复抽样1000次作为验证组,首先采用单因素分析筛选不明原因不孕患者优质囊胚形成与否的影响因素,然后采用套索算法(LASSO)挑选出最佳匹配因素后,纳入多因素向前逐步Logistic回归找出其独立影响因素并绘制列线图,最后采用受试者工作曲线、校准曲线、临床决策曲线、临床影响曲线对该预测模型进行区分度与准确度及临床应用效能进行验证。结果与结论:①单因素分析不明原因不孕患者优质囊胚形成与否的影响因素为年龄、授精方式、抗苗勒管激素水平、基础卵泡刺激素水平、基础促黄体生成素水平、人绒毛膜促性腺激素注射日卵泡刺激素水平、人绒毛膜促性腺激素注射日雌二醇水平、人绒毛膜促性腺激素注射日孕酮水平、第3天优胚数、囊胚培养数(P<0.05);②通过LASSO回归进一步筛选出的最佳匹配因素为年龄、授精方式、抗苗勒管激素水平、基础促黄体生成素水平、人绒毛膜促性腺激素注射日卵泡刺激素水平、人绒毛膜促性腺激素注射日雌二醇水平、第3天优胚数、囊胚培养数(P<0.05);多因素向前逐步Logistic回归结果显示年龄、授精方式、抗苗勒管激素水平、第3天优胚数、囊胚培养数为不明原因不孕患者优质囊胚形成与否的独立影响因素;③受试者工作曲线显示,模型组曲线下面积为0.880(0.834,0.926),验证组曲线下面积为0.889(0.859,0.918);说明该预测模型具有较好的区分度;校准曲线平均绝对误差为0.036,表示该模型具有较好的准确性;Hosmer-Lemeshow检验表明该模型预测形成优质囊胚的概率与实际优质囊胚形成的概率无统计学差异(P>0.05);临床决策曲线与临床影响曲线显示,模型组与验证组分别在阈概率值为0.16-0.96与0.08-0.93时具有临床最大净获益,且在该阈概率范围内具有较好的临床应用效能。结果表明,年龄、授精方式、抗苗勒管激素水平、第3天优胚数、囊胚培养数为不明原因不孕症患者优质囊胚形成与否的独立影响因子,通过其构建的临床预测模型列线图具有较好的临床预测价值与临床应用效能,可为临床预后与干预及制定个体化医疗方案提供依据。

第3天新鲜胚胎移植周期中卵裂球数目与助孕方式对妊娠结局的影响

目的探讨第3天新鲜胚胎移植周期中卵裂球数目及助孕方式对妊娠结局的影响。方法回顾性分析2012年1月至2020年8月海军军医大学(第二军医大学)第一附属医院生殖医学中心收治的首次接受胚胎移植、采用常规体外受精(IVF)或卵胞浆内单精子显微注射技术(ICSI)助孕、胚胎质量为Ⅰ级或Ⅱ级的患者资料。共1788个第3天新鲜移植周期纳入研究,先分为单胚胎移植和双胚胎移植两大类,每类再根据卵裂球数目分为≤6个细胞组、7个细胞组、8个细胞组、9个细胞组、≥10个细胞组。在新鲜单胚胎移植周期中,≤6个细胞组36个(IVF 21个、ICSI 15个),7个细胞组53个(IVF 25个、ICSI 28个),8个细胞组204个(IVF 146个、ICSI 58个),9个细胞组36个(IVF 22个、ICSI 14个),≥10个细胞组50个(IVF 34个、ICSI 16个);在新鲜双胚胎移植周期中,≤6个细胞组59个(IVF 27个、ICSI 32个),7个细胞组72个(IVF 48个、ICSI 24个),8个细胞组1178个(IVF 820个、ICSI 358个),9个细胞组44个(IVF 24个、ICSI 20个),≥10个细胞组56个(IVF 24个、ICSI 32个)。比较各组的胚胎种植率、临床妊娠率、流产率和活产率。结果在新鲜单胚胎移植周期中,8个细胞组的胚胎种植率、临床妊娠率高于≤6个细胞组、7个细胞组、9个细胞组、≥10个细胞组(均P<0.05),活产率高于≤6个细胞组、7个细胞组(均P<0.05),流产率与≤6个细胞组、7个细胞组、9个细胞组、≥10个细胞组比较差异无统计学意义(均P>0.05);8个细胞组中ICSI助孕的胚胎移植后胚胎种植率、临床妊娠率、活产率均高于IVF助孕(均P<0.05),而≤6个细胞组、7个细胞组、9个细胞组、≥10个细胞组中IVF和ICSI 2种助孕方式的胚胎种植率、临床妊娠率、活产率差异均无统计学意义(均P>0.05)。在新鲜双胚胎移植周期中,8个细胞组的胚胎种植率、临床妊娠率、活产率均高于≤6个细胞组、7个细胞组、9个细胞组、≥10个细胞组(均P<0.05),流产率与≤6个细胞组、7个细胞组、≥10个细胞组比较差异无统计学意义(均P>0.05),但低于9个细胞组且差异有统计学意义(P<0.05);≤6个细胞组ICSI助孕的胚胎移植后胚胎种植率、临床妊娠率、活产率均高于IVF助孕(均P<0.05),而7个细胞组、8个细胞组、9个细胞组、≥10个细胞组中IVF和ICSI 2种助孕方式的胚胎种植率、临床妊娠率、活产率差异均无统计学意义(均P>0.05)。结论在第3天新鲜胚胎移植周期中,可首选8个细胞胚胎,其次是9个细胞胚胎、≥10个细胞胚胎、7个细胞胚胎、≤6个细胞胚胎;8个细胞胚胎在ICSI助孕方式下的胚胎种植率、临床妊娠率和活产率比IVF高,可以优先选择;对于一部分ICSI助孕患者在无其他优质胚胎情况下,移植≤6个细胞的胚胎也可以获得较好的妊娠结局。

宫腔粘连术后胚胎移植活产的影响因素

目的探讨宫腔粘连分离术后胚胎移植助孕活产的预后因素。方法回顾性分析宫腔镜检查诊断宫腔粘连(intrauterine adhesion,IUA)并行宫腔粘连分离术,于2018年1月~2020年12月行胚胎移植共643例资料。比较术后治疗方案及胚胎移植后的妊娠结局。以活产率为主要终点指标,并对相关因素进行回归分析,探讨影响活产的因素。结果643例中,宫腔粘连为轻度20.5%(132/643),中度63.6%(409/643),重度15.9%(102/643)。宫腔镜术后至第一周期胚胎移植的中位时间为126(73,225)d。临床妊娠率32.7%(210/643),活产率24.7%(159/643)。logistic回归分析显示,年龄(OR=0.926,95%CI:0.880~0.974,P=0.003)和移植日子宫内膜厚度(OR=1.188,95%CI:1.030~1.370,P=0.018)是活产的预后因素。轻度粘连组和中度粘连组中年龄增大活产率显著降低(P=0.004、0.018),重度粘连组随着年龄增加活产率降低,但差异无显著性(P=0.526)。术后雌激素用量、人工周期数目、手术与移植间隔时间、新鲜或冻融胚胎移植、移植的胚胎类型对活产无显著影响。结论年龄和移植日子宫内膜厚度是宫腔粘连术后胚胎移植活产的预后因素。宫腔粘连术后新鲜胚胎移植或冻融胚胎移植、术后至胚胎移植间隔时间对活产结局无显著影响。

低体质指数不利于不明原因原发不孕患者人工授精诱导排卵周期妊娠结局

【目的】探索女方体质指数(BMI)对不明原因原发不孕女性人工授精诱导排卵周期(OI-IUI)妊娠结局的影响。【方法】回顾性分析2016年1月至2022年12月于中山大学孙逸仙纪念医院生殖中心行OI-IUI助孕的不明原因原发不孕夫妻共764个周期的临床资料。按照女方患者BMI分为3组,低BMI组(消瘦,BMI<18.5 kg/m^(2))、正常BMI组(正常体质量,18.5 kg/m^(2)≤BMI<23.0 kg/m^(2))、高BMI组(超重、肥胖,BMI≥23.0 kg/m^(2)),比较各组间一般资料以及妊娠结局。采用单因素分析和Logistic回归分析矫正混杂因素,探讨BMI与OI-IUI活产率的相关性。【结果】三组HCG阳性率(7.08%、9.74%、13.19%)、宫内妊娠率(5.51%、7.91%、13.19%)和活产率(4.72%、6.90%、12.50%)由低BMI组到高BMI组依次递增,早期流产率(14.28%、10.26%、5.26%)则是由低BMI组至高BMI组依次递减,其中高BMI组活产率明显高于低BMI组及正常BMI组,差异有统计学意义(P=0.034)。根据二元Logistic回归分析显示,BMI是影响活产的独立影响因素,与低BMI相比,高BMI可提高活产率(OR=3.15,95%CI=1.191,8.329,P=0.021)。【结论】低BMI不利于不明原因原发不孕女性OI-IUI妊娠结局,对该部分患者鼓励以健康方式进行合理增重。

IVF/ICSI-ET中胚胎实时监测系统与常规形态学评估选择性单胚胎移植累积活产率分析

目的:分析胚胎实时监测(TLM)系统和常规形态学评估(CMA)在体外受精/卵胞浆内单精子注射-胚胎移植(IVF/ICSI-ET)中选择性单胚胎移植的临床应用价值,并初步探讨拉曼光谱分析胚胎培养液对临床妊娠率的预测价值。方法:本研究为前瞻性随机对照临床研究,选择2019年4月至2020年7月在苏州市立医院生殖与遗传中心行IVF/ICSI-ET助孕的139例患者,随机分为TLM组和CMA组,分别选择最优胚胎行单胚胎移植(新鲜周期和复苏周期),患者第1次胚胎移植未获临床妊娠,则进行第2次,比较两组患者移植后的累积活产率和其他妊娠结局差异。同时收集IVF/ISCI受精后第3天胚胎培养液15μl,进行拉曼光谱分析。结果:TLM组与CMA组的累积活产率、累积临床妊娠率、累积早产率、累积早期自然流产率、累积异位妊娠率、累积早产率、小于胎龄儿或大于胎龄儿差异均无统计学意义(P>0.05)。TLM组新生儿性别比低于CMA组,但差异无统计学意义(P>0.05)。胚胎培养液拉曼光谱分析预测临床妊娠率的准确度为67.21%。结论:在卵巢储备功能良好的年轻女性中,进行选择性单胚胎移植时TLM评估胚胎优势不明显,需警惕基于动力学参数的胚胎选择可能影响性别比。拉曼光谱分析胚胎培养液尚不能很好地预测胚胎的种植能力。