| Objective:The IVF/ICSI outcomes of couples with abnormal karyotype and AZF microdeletion in male were retrospectively analyzed to study the effects of these genetic abnormalities on fertility and offspring health.In addition,the research aims to explore the related factors of healthy live birth in infertile man undergoing IVF/ICSI,and to provide reference and guidance for the clinical consultation and treatment of infertile man by assisted reproductive technology.This study is divided into the following parts.1.Effect of karyotype abnormalities in infertile men on IVF/ICSI outcomes.2.Effect of AZF microdeletion in infertile men on IVF/ICSI outcomes.3.Effect of AZF microdeletion combined with karyotype abnormalities in infertile men on IVF/ICSI outcomes.4.Study of factors associated with healthy live birth in infertile men undergoing IVF/ICSI.The research mainly involves the following key indicators of IVF/ICSI: 1.Laboratory and pregnancy outcome indicators,including fertilization rate,2PN fertilization rate,2PN cleavage rate,high-quality embryo rate,blastocyst formation rate,available blastocyst formation rate,biochemical pregnancy rate,clinical pregnancy rate,implantation rate and early abortion rate.2.Delivery and offspring birth outcome indicators,including average gestational age,delivery rate,premature birth rate,twin rate,birth weight,live birth rate,perinatal mortality,birth defect rate.1.Effect of karyotype abnormalities in infertile men on IVF/ICSI outcomesMethods: From January 2012 to December 2019,infertile couples were selected who were treated with IVF or ICSI for the first time in the center of reproductive medicine and prenatal genetics of the first hospital of Jilin University.According to the corresponding screening criteria,2800 couples were included.According to whether the karyotype of male chromosome is abnormal,the patients were divided into chromosome abnormalities group(46 pairs),chromosomal polymorphism group(136 pairs)and normal chromosome group(2618 pairs).The differences of laboratory and pregnancy outcome,delivery and offspring birth outcome were analyzed and compared between these groups.Results:(1)The fertilization rate of chromosome abnormalities group was significantly lower than that of normal chromosome group(71.18% vs 78.55%,P < 0.05),the rate of high quality embryo and biochemical pregnancy in chromosome abnormalities group was significantly higher than that of normal chromosome group(58.90% vs 49.25%,78.57% vs 63.24%,P < 0.05),and there was no statistical difference between other laboratory and pregnancy indicators(P > 0.05).Among the different types of chromosomal abnormalities,the fertilization rate of chromosomal numerical abnormality and chromosomal structural abnormality were significantly lower than that of normal chromosomal group(72.12%,69.18%,vs 78.55%,P < 0.05),the high-quality embryo rate of chromosomal numerical abnormality and chromosomal structural abnormality were significantly higher than that of normal chromosomal group(59.11%,58.43%,vs 49.25%,P < 0.05),and there was no significant difference in other laboratory and pregnancy indicators(P > 0.05).(2)There was no significant difference in the laboratory and pregnancy indicators between chromosomal polymorphism group and normal chromosome group(P > 0.05).Among the different types of chromosomal polymorphism,the fertilization rate of D/G group was significantly lower than that of normal chromosome group(74.64% vs 78.55%,P < 0.05),and the fertilization rate and 2PN fertilization rate of Y chromosomal polymorphism group were significantly higher than those of control group(84.66% vs 78.55%,78.41% vs 65.99%,P < 0.05).There was no significant difference in other laboratory and pregnancy indicators(P > 0.05).(3)There was no significant difference in the delivery and offspring birth outcome indicators between chromosome abnormalities group and normal chromosome group(P > 0.05).There was no significant difference between chromosomal numerical abnormality group,chromosomal structural abnormality group and the normal chromosome group(P > 0.05).(4)There was no significant difference in the delivery and offspring birth outcome indicators between chromosomal polymorphism group and normal chromosome group(P > 0.05).Among the different types of chromosome polymorphism,the birth defect rate of chromosome 9 inversion group was statistically higher than that of normal chromosome group(18.18%(2[twin births,hip dysplasia]/11)vs 1.61%(23/1433),P < 0.05),and there was no significant difference in other indicators(P > 0.05).Conclusion:(1)Chromosomal numerical abnormality and chromosomal structural abnormality both have negative effect on IVF/ICSI fertilization,but have no effect on embryo development quality,embryo development potential and clinical pregnancy outcome.(2)On the whole,chromosome polymorphism had no significant negative effect on IVF/ICSI fertilization,embryo development quality,embryo development potential and clinical pregnancy outcome.But abnormalities in the D/G group may reduce the fertilization rate.(3)Chromosomal numerical abnormality,chromosomal structural abnormality,chromosomal polymorphism and its different types had no significant effect on delivery and offspring birth outcomes of IVF/ICSI.2.Effect of AZF microdeletion in infertile men on IVF/ICSI outcomesMethods: From January 2012 to December 2019,infertile couples were selected who were treated with IVF or ICSI for the first time in the center of reproductive medicine and prenatal genetics of the first hospital of Jilin University.A total of 921 couples were included according to the corresponding screening criteria.The couples were divided into AZF microdeletion group(143 pairs)and AZF normal group(778 pairs)according to whether they had AZF microdeletion or not.The differences of laboratory and pregnancy outcome,delivery and offspring birth outcome were analyzed and compared between these groups.Results:(1)There was no significant difference in laboratory and pregnancy indicators between AZF microdeletion group and AZF normal group(P > 0.05).(2)In different types of microdeletions in AZFc region,the fertilization rate,2PN fertilization rate,blastocyst formation rate and implantation rate of gr/gr deletion group were significantly higher than those of AZF normal group(83.37% vs 77.25%,77.68% vs 69.02%,43.56% vs 33.47%,62.16% vs 43.28%,P < 0.05).The 2PN fertilization rate of b1/b3 deletion group was significantly lower than that of AZF normal group(57.63%(68/118)vs 69.02%(5771/8361),P < 0.05).(3)In different semen quality groups,the fertilization rate and 2PN fertilization rate of AZF microdeletion group were significantly lower than those of AZF normal group in azoospermia patients(58.42% vs 77.31%,54.46% vs 70.37%,P < 0.05).The fertilization rate and biochemical pregnancy rate of AZF microdeletion group were significantly lower than those of AZF normal group in severe oligozoospermia patients(74.71% vs 78.30%,60.00% vs 73.33%,P < 0.05).All laboratory and pregnancy indicators in the AZF microdeletion group of patients with oligozoospermia were not statistically different from those in the AZF normal group.The fertilization rate and 2PN fertilization rate of AZF microdeletion group were higher than those of AZF normal group in patients with normal sperm concentration(83.99% vs 76.57%,70.68% vs 64.07%,P < 0.05).(4)There was no significant difference in delivery and offspring birth outcomes between AZF microdeletion group and AZF normal group(P > 0.05).The indicators of delivery and offspring birth outcomes in the different microdeletion types in the AZFc region were not statistically different from the AZF normal group(P > 0.05).(5)There was no statistical difference in the delivery and offspring birth outcome indicators between the AZF microdeletion group and the AZF normal group among different semen quality groups(P > 0.05).Conclusion:(1)Overall,AZF microdeletions have no negative effect on IVF/ICSI fertilization,embryo development quality,embryonic development potential and clinical pregnancy outcome.However,b1/b3 deletion of AZFc region may reduce the normal fertilization rate.(2)AZF microdeletion affects IVF/ICSI fertilization in infertile men with different semen quality and negatively affects fertilization rates in patients with azoospermia and severe oligospermia.(3)AZF microdeletions and different microdeletion types in the AZFc region all had no significant effect on IVF/ICSI delivery and offspring birth outcomes.(4)AZF microdeletion had no significant effect on delivery and offspring birth outcomes in infertile men with different semen quality.3.Effect of AZF microdeletion combined with karyotype abnormalities in infertile men on IVF/ICSI outcomesMethods: From January 2012 to December 2019,infertile couples were selected who were treated with IVF or ICSI for the first time in the center of reproductive medicine and prenatal genetics of the first hospital of Jilin University.A total of 930 couples were included according to the corresponding screening criteria.The patients were divided into AZF microdeletion combined with karyotype abnormalities group(12 pairs),abnormal karyotype alone group(57 pairs),AZF microdeletion alone group(140 pairs),and both AZF and karyotype normal group(721 pairs)according to the results of AZF and karyotype analysis.The differences of laboratory and pregnancy outcome,delivery and offspring birth outcome were analyzed and compared between these groups.Results:(1)The rates of high-quality embryos,blastocyst formation,available blastocyst formation,and biochemical pregnancy in the AZF microdeletion combined with karyotype abnormalities group were statistically significantly lower than those in the AZF microdeletion alone,abnormal karyotype alone,and both AZF and karyotype normal groups(34.44% vs 57.24%,47.27%,48.30%;34.48% vs 50.47%,51.78%,49.69%;18.97% vs 35.05%,35.04%,33.47%;41.67% vs 73.68%,68.57%,68.52%,P < 0.05).(2)The clinical pregnancy and implantation rates in the AZF microdeletion combined with karyotype abnormalities group showed a trend toward lower rates compared with abnormal karyotype alone group,AZF microdeletion alone group,and both AZF and karyotype normal group,although there was no statistical difference(P > 0.05)(clinical pregnancy rate 41.67% vs.64.91%,60.00%,60.19%;implantation rate(33.33% vs 48.62%,41.90%,43.28%).(3)There was no significant difference in the delivery and offspring birth outcome indicators between AZF microdeletion combined with karyotype abnormalities group and AZF microdeletion alone group,abnormal karyotype alone group,and AZF and karyotype normal group(P > 0.05).Conclusion:(1)AZF microdeletions combined with abnormal karyotype has no significant effect on IVF/ICSI fertilization in infertile men and has a negative effect on embryo development quality and embryo development potential.There may be a negative impact on clinical pregnancy outcome.(2)AZF microdeletions combined with abnormal karyotype has no significant effect on IVF/ICSI delivery and offspring birth outcomes.4.Study of factors associated with healthy live birth in infertile men undergoing IVF/ICSIMethods: From January 2012 to December 2019,infertile couples were selected who were treated with IVF or ICSI for the first time in the center of reproductive medicine and prenatal genetics of the first hospital of Jilin University.A total of 2766 couples were included as subjects according to the corresponding screening criteria.The patients were divided into two groups according to whether they had a healthy live birth outcome.A Logistic univariate analysis was performed to screen out statistically significant factors,followed by a Logistic multivariate analysis to uncover statistically significant variables to introduce into the regression equation to construct an assessment model of healthy live birth outcomes in infertile men and plot the nomogram.Results:(1)Univariate Logistic analysis showed that female age,male age,years of infertility,factors of infertility,type of infertility of woman,type of infertility of man,number of antral follicles(AFC)and body mass index of woman,estradiol level on day of HCG,number of high-quality embryos,basic FSH of woman,semen quality,number of transferred embryos,endometrial thickness on the day of embryo transfer,type of transfer cycle and type of transferred embryos were variables associated with healthy live birth outcome(P < 0.05).Karyotype abnormalities and AZF microdeletions in men did not correlate statistically with healthy live birth outcome(P > 0.05).(2)Multivariate Logistic analysis showed that female age,semen quality,number of retrieved oocytes,number of high-quality embryos,type of transfer cycle,number of transferred embryos,type of transferred embryo and endometrial thickness on the day of embryo transfer(P < 0.05)were independent factors associated with healthy live birth outcome(P < 0.05).(3)The evaluation model P of healthy live birth outcome was constructed as follows: P = 1 /(1 + exp(-y)),where y=-0.616×(female age <35=1,35≤age<40=2,≥40=3)+(normal sperm concentration=0,azoospermia=0.331,severe oligospermia =0.186,oligozoospermia =-0.210)+ 0.083×(number of high-quality embryos,>15 counted as 15)+(frozen-thaw transfer =0.333,fresh transfer = 0)+(number of embryos transferred 1 = 0,2 = 0.598,3 = 0.250)+(blastocysts = 0.482,cleavage embryos = 0)+(endometrial thickness on the day of embryo transfer ≤6 mm = 0,7-10 mm = 2.017,≥11 mm = 2.586)-2.847.This model was tested for likelihood ratio and the regression equation was statistically significant(= 252.6,P < 0.001).Area under ROC curve = 0.665,95% CI: 0.644-0.685,P value < 0.001.P=0.433 was used as the diagnostic cut-off point,corresponding to a sensitivity of 69% and a specificity of 56%.Nomogram was drawn based on the regression model with a C-index of 0.665,and calibration curves showed good agreement between the estimated probability of healthy live births and the true frequency of occurrence based on the constructed nomogram.Conclusion:(1)The main factors affecting the IVF/ICSI outcome of healthy live birth in infertile men were found.(2)The female age was the unfavorable factor to the outcome of healthy live birth.(3)The number of high-quality embryos,transferred two embryos,the endometrial thickness on the day of embryo transfer,azoospermia,frozen-thaw transfer and blastocyst transfer were the favorable factors of healthy live birth outcome.(4)The evaluation model of IVF/ICSI healthy live birth for infertile men was successfully constructed.The nomogram for predicting the probability of healthy live birth was drawn. |
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