Infertility and Assisted
Reproductive Technologies
不孕症和 辅助生殖技术
XIN LU
Obstetrics & Gynecology Hospital
Fudan University
2006-3-1
Contents
? Infertility
? Definition;
? Causes;
? Examinations and Diagnosis;
? Treatment;
? Assisted Reproductive Technologies (ART) ;
? Intrauterine insemination ( IUI);
? In vitro fertilization and embryo transfer (IVF-ET);
? Intracytoplasmic sperm injection (ICSI);
? Gamete intrafallopian transfer (GIFT);
DEFINITION of Infertility
不孕症定义
What is Infertility?
Infertility is defined two years of unprotected
intercourse without pregnancy.
(WHO,one year)
Primary Infertility, no previous pregnancies
原发不孕 have occurred;
Secondary Infertility,a prior pregnancy has
继发不孕 occurred;
Age and Infertility 年龄与不孕
? age fertility abortion
? Fertility rate <30 yr 74% 11.9%
per 1,000 30-35 yr 62% 15.0%
>35 yr 54% 24.6%
>40 yr 51.0%
female male
10 20 30 40 50 60 70
Female Reproductive duct
anatomy 女性生殖道解剖
Female
ovary 卵巢
fallopian 输卵管
uterus 子宫
cervix 宫颈
Vagina 阴道
Male Reproductive duct
anatomy 男性生殖道解剖
Male
testis 睾丸
epididymis 附睾,
prostate 前列腺
vas deferens 输精管
seminal vesicals 精囊
bulbourethral glands 尿道球腺
ejaculatory duct 射精管
urethra 尿道
Female Reproductive
Physiology 女性生殖生理
? 1,下丘脑 -垂体 -卵巢轴内分泌调节 Femal Male
( H-P-O) (H-P-T)
GnRH GnRH
FSH,LH FSH,LH
E/P T
4,3.输卵管
2,卵巢周期性排卵 5,宫颈
6,下生殖道
hypothalamus
ovary
pituitary
子宫 ovary4.
子宫
Normal Gestation
-----the beginning of human
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
sperm
Causes 原因
Causes Percentage
Female factors 40-55 %
Male factors 25-40 %
Both male and
female factors 20 %
Immunologic
unexplained factors 10 %
Female Factors 女方因素
Ovulatory dysfunction
（ 排卵障碍 ）
Pelvic factors
（ 盆腔因素 ）
1,Hypothalamic dysfunction;
2,Pituitary Insufficiency;
3,Ovarian factor (peripheral defect);
4,Others,thyroid or adrenal dysfunction;
Ovulatory dysfunction
排卵障碍
hypothalamus
pituitary
ovary
Pelvic factors 盆腔因素
1,Tubal factors,
injury,blockage,adhesion;
2,Uterine factors:
cogenital anatomic abnormalities;
endometrium disorder,tumor;
3,Cervical factors:
Infection,cogenital abnormalities;
4,Extra-genital tract factors;
Infection,cogenital abnormalities;
Female Factors
Summary
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
sperm
Hypothalamus
Pituitary
Thyroid Adrenal
Male Factors 男方因素
1,Abnormal spermatogenesis
congenital;
chronic diseases;
infectious factors;
2,Obstructive,sperm transport
abnormalities;
3,Immunologic factors;
4,Endocrine disorders;
5,Sexual dysfunction;
Both Male and Female Factors
1,No demonstrable cause;
2,Psychological factors;
3,Immunologic factors;
count for 10%;
autoimmune response;
auto-antibodies;
Summary--Infertility Causes
Factors from either or both partners may
contribute to difficulties in conceiving;
THEREFORE
It is important to consider all possible
diagnosis before pursuing invasive treatment.
Examination and Diagnoses
检查和诊断
? Initial Visit 初诊
? The initial visit is the most important;
? The infertility is a problem of couple;
? The male partner should be present;
? History,both male and female;
? The guide to diagnostic and treatment plans;
Examinations 检查
? Female
? Physical examination;
? Bimanual examination（ 双合诊） ;
? Rectal-Vaginal-examination (三合诊）；
? Laboratory;
? Assistant imaging;
? Male
? Physical examination;
? Laboratory-Semen analysis;
Examinations (for female)
女方检查
? Special Laboratory Examinations:
semen analysis（ 精液分析） ;
hormone measurement;
sperm penetration assay (SPA)精子穿透试验 ;
postcoital examinition of cervical mucus
（性交后宫颈粘液试验）
anti-sperm immunologic examination;
? Assistant imaging,
Unltrasound 超声 ;
Hysterosalpingogram 子宫输卵管碘油造影 ;
Hysteroscopy 宫腔镜 ;
? Laparoscopy 腹腔镜；
Examination and Diagnoses
Initial evaluation
History
Physical exam
Irregular menses
No ovulation
HSG or
Hysteroscopy
Abnormal of
uterine
Normal
evaluation
HSG
Tubal blockage
Abnormal
Semen
analysis
anovulation Tubal factor unexplained Uterine factor Male factor
Further Investigate and Treatment
Normal Values for Semen Analysis
精液分析正常值
volume ≥ 2.0 mL
sperm concentration ≥ 20 x 106 /mL
motility ≥ 50 %
normal morphology ≥ 15 %
WBC < 106 /mL
Data from WHO,1999
Please keep in mind:
1,Cycle of Spermiogenesis takes about 74 days;
2,Semen parameters in males may vary;
3,Abnormal semen analysis should repeat at least once;
Methods to monitor ovulation
监测排卵的方法
? Luteinizing Hormone monitoring,
LH surge;
after 34-36 hr occur ovulation;
? Basal Body Temperature,
simple,cheap,biphasic pattern;
? Mid-luteal serum progesterone,> 3ng/mL,peak;
? Premenstrual molimina,95% presence;
? Mucus change,thick and cellular,no crystalline fern;
? Ultrasound monitoring,
follicle size 21-23 mm,fluid in the cul-de-sac.
Treatment principle for
female factors
Causes Treatment
induction of ovulation；
tuboplasty,
microsurgery；
medication or surgery；
immune inhibition；
anovulation
Tubal factor
Anatomic factor
immunologic
azoospermia
genetic disease
after surgery
Failure above
Assisted Reproductive Technologies
(ART) 辅助生育技术unexplained
Induction of ovulation
诱发排卵 -1
1,Clomiphen 氯米芬,ER binding GnRH,FSH/LH
dosage,50 mg,period day 5th,5 days；
2,Gonadotropin therapy 促性腺激素治疗：
Indications,Hypogonadotropic hypogonadism;
Pituitary dysfunction;
COH in IVF;
(COH, controlled ovarian hyperstimulation)
HMG,human menopausal gonadotropins;
FSH 75 IU/LH 75 IU,IM or SC;
Recombinant FSH,75 IU,SC;
3,HCG 绒毛膜促性腺腺激素, 5000-10000 IU;
Induction of ovulation
诱发排卵 -2
4,Gonadotropin releasing hormone agonist
(GnRH-a),hypothalamic factor,as COH;
protocol,according the every GnRH-a
component and feature,the time of
start and discontinuation are different;
zoladex; decapeptyl,dipherenline,
enantone;
5,GnRH antagonist;
6,Bromocriptine 溴隐停, high PRL;
Assisted Reproductive
Technologies (ART) 辅助生育技术
? Intrauterine insemination ( IUI);
宫腔内人工授精 ;
? In vitro fertilization and embryo transfer
(IVF-ET); 体外受精与胚胎移植 ;
? Intracytoplasmic sperm injection (ICSI);
单精子卵泡浆注射；
? Gamete intrafallopian transfer (GIFT);
配子输卵管移植 ;
Intrauterine insemination
( IUI) 人工授精
? Indications:
1,as treatment of male factor infertility;
2,psychological factors;
3,unexplained infertility;
4,genetic defects;
? Types:
1,artificial insemination with husband’s sperm (AIH);
2,artificial insemination by donor (AID);
? Method:
placement of about 0.3 ml of washed,processed
and concentrated sperm into the intrauterine cavity
by trans-cervical catheterizaion.
In vitro fertilization and embryo
transfer (IVF-ET) 体外受精与胚胎移植
? Indications:
1,tubal factor;
2,endometriosis;
3,unexplained infertility;
4,IUI failure;
5,Immunologic factors;
? Method:
1,Superovulation,COH,GnRH-a/FSH(HMG)/HCG;
2,Aspiration of eggs;
3,Fertilization with capacitated sperm;
4,Culture of fertilized egg in the lab;
5,Replacement of fertilized egg into the uterus;
Gamete intrafallopian
transfer (GIFT) 配子输卵管移植
? Indications:
1,unexplained infertility;
2,endometriosis;
3,IUI failure;
4,Premature ovarian failure (POF);
5,Immunologic factors;
? Method:
1,Superovulation is induced as IVF-ET;
2,HCG injection is given;
3,Follicle are aspirated via laparoscopy;
4,Sperm mixed with egg;
5,Replacement of fertilized egg into fallopian tube;
ART Complications
辅助生育技术并发症
? Multiple gestations 多胎妊娠 ;
? Pre-eclampsia 产前子痫 ;
? Ovarian hyperstimulation syndrome (OHSS)
卵巢过激综合征 ;
? Premature birth 早产 ;
? Low birth weight 出生低体重 ;
? Long term emotional,social and psychological
impact 长期影响（情绪，社会，精神） ;
复习思考题
? 1,不孕症应如何进行诊断 ；
? 2,女性不孕的特殊检查有哪些；
习题练习
1,WHO 有关原发不孕症的定义哪个是正确的？
A,性生活正常，未避孕，结婚 3年未孕；
B,性生活正常，未避孕，结婚 2年未孕；
C,性生活正常，避孕，结婚 1年未孕；
D,性生活正常，未避孕，结婚 1年未孕；
E,性生活异常，未避孕，结婚 2年未孕；
习题练习
2,下列有关精液检查哪个是错误的？
A,精液量 3 mL；
B,PH 7.2；
C.室温下 40 分钟液化；
D,精子浓度 5.5X107；
E,精子畸形率 10%；
习题练习
3,28岁，已婚，结婚 2年未孕；月经规则，经期
腹痛 5年，男方体健。妇科检查：子宫大小正
常，后倾，不活动，压痛，双侧附件可触及
6cm囊块； BBT 双相，根据上述症状体征，
考虑不孕的原因是：
A,慢性盆腔炎；
B,结核性盆腔炎；
C,子宫内膜异位症；
D,卵巢癌；
E,输卵管积水；
习题练习
4,32岁，已婚，结婚 2年未孕；月经周期规则，但
间隔时间短，要检查黄体功能异常，下列哪项对
诊断无帮助：
A,诊断性刮宫（月经前）；
B,BBT 测定；
C,血雌激素水平测定；
D,血孕激素测定；
E,血 LH水平测定；
习题练习
5,28岁，已婚，结婚 8年,G3P0,不孕 2年；慢性下
腹痛 4年；月经规则，经量正常，男方体健。妇科
检查：子宫大小正常，双侧附件增厚；内分泌检
查在正常范围，根据上述症状体征，首先进行的
不孕的检查是：
A,BBT；
B,诊断性刮宫 ；
C,宫腔镜；
D,腹腔镜；
E,子宫输卵管碘油造影；
Reproductive Technologies
不孕症和 辅助生殖技术
XIN LU
Obstetrics & Gynecology Hospital
Fudan University
2006-3-1
Contents
? Infertility
? Definition;
? Causes;
? Examinations and Diagnosis;
? Treatment;
? Assisted Reproductive Technologies (ART) ;
? Intrauterine insemination ( IUI);
? In vitro fertilization and embryo transfer (IVF-ET);
? Intracytoplasmic sperm injection (ICSI);
? Gamete intrafallopian transfer (GIFT);
DEFINITION of Infertility
不孕症定义
What is Infertility?
Infertility is defined two years of unprotected
intercourse without pregnancy.
(WHO,one year)
Primary Infertility, no previous pregnancies
原发不孕 have occurred;
Secondary Infertility,a prior pregnancy has
继发不孕 occurred;
Age and Infertility 年龄与不孕
? age fertility abortion
? Fertility rate <30 yr 74% 11.9%
per 1,000 30-35 yr 62% 15.0%
>35 yr 54% 24.6%
>40 yr 51.0%
female male
10 20 30 40 50 60 70
Female Reproductive duct
anatomy 女性生殖道解剖
Female
ovary 卵巢
fallopian 输卵管
uterus 子宫
cervix 宫颈
Vagina 阴道
Male Reproductive duct
anatomy 男性生殖道解剖
Male
testis 睾丸
epididymis 附睾,
prostate 前列腺
vas deferens 输精管
seminal vesicals 精囊
bulbourethral glands 尿道球腺
ejaculatory duct 射精管
urethra 尿道
Female Reproductive
Physiology 女性生殖生理
? 1,下丘脑 -垂体 -卵巢轴内分泌调节 Femal Male
( H-P-O) (H-P-T)
GnRH GnRH
FSH,LH FSH,LH
E/P T
4,3.输卵管
2,卵巢周期性排卵 5,宫颈
6,下生殖道
hypothalamus
ovary
pituitary
子宫 ovary4.
子宫
Normal Gestation
-----the beginning of human
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
sperm
Causes 原因
Causes Percentage
Female factors 40-55 %
Male factors 25-40 %
Both male and
female factors 20 %
Immunologic
unexplained factors 10 %
Female Factors 女方因素
Ovulatory dysfunction
（ 排卵障碍 ）
Pelvic factors
（ 盆腔因素 ）
1,Hypothalamic dysfunction;
2,Pituitary Insufficiency;
3,Ovarian factor (peripheral defect);
4,Others,thyroid or adrenal dysfunction;
Ovulatory dysfunction
排卵障碍
hypothalamus
pituitary
ovary
Pelvic factors 盆腔因素
1,Tubal factors,
injury,blockage,adhesion;
2,Uterine factors:
cogenital anatomic abnormalities;
endometrium disorder,tumor;
3,Cervical factors:
Infection,cogenital abnormalities;
4,Extra-genital tract factors;
Infection,cogenital abnormalities;
Female Factors
Summary
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
sperm
Hypothalamus
Pituitary
Thyroid Adrenal
Male Factors 男方因素
1,Abnormal spermatogenesis
congenital;
chronic diseases;
infectious factors;
2,Obstructive,sperm transport
abnormalities;
3,Immunologic factors;
4,Endocrine disorders;
5,Sexual dysfunction;
Both Male and Female Factors
1,No demonstrable cause;
2,Psychological factors;
3,Immunologic factors;
count for 10%;
autoimmune response;
auto-antibodies;
Summary--Infertility Causes
Factors from either or both partners may
contribute to difficulties in conceiving;
THEREFORE
It is important to consider all possible
diagnosis before pursuing invasive treatment.
Examination and Diagnoses
检查和诊断
? Initial Visit 初诊
? The initial visit is the most important;
? The infertility is a problem of couple;
? The male partner should be present;
? History,both male and female;
? The guide to diagnostic and treatment plans;
Examinations 检查
? Female
? Physical examination;
? Bimanual examination（ 双合诊） ;
? Rectal-Vaginal-examination (三合诊）；
? Laboratory;
? Assistant imaging;
? Male
? Physical examination;
? Laboratory-Semen analysis;
Examinations (for female)
女方检查
? Special Laboratory Examinations:
semen analysis（ 精液分析） ;
hormone measurement;
sperm penetration assay (SPA)精子穿透试验 ;
postcoital examinition of cervical mucus
（性交后宫颈粘液试验）
anti-sperm immunologic examination;
? Assistant imaging,
Unltrasound 超声 ;
Hysterosalpingogram 子宫输卵管碘油造影 ;
Hysteroscopy 宫腔镜 ;
? Laparoscopy 腹腔镜；
Examination and Diagnoses
Initial evaluation
History
Physical exam
Irregular menses
No ovulation
HSG or
Hysteroscopy
Abnormal of
uterine
Normal
evaluation
HSG
Tubal blockage
Abnormal
Semen
analysis
anovulation Tubal factor unexplained Uterine factor Male factor
Further Investigate and Treatment
Normal Values for Semen Analysis
精液分析正常值
volume ≥ 2.0 mL
sperm concentration ≥ 20 x 106 /mL
motility ≥ 50 %
normal morphology ≥ 15 %
WBC < 106 /mL
Data from WHO,1999
Please keep in mind:
1,Cycle of Spermiogenesis takes about 74 days;
2,Semen parameters in males may vary;
3,Abnormal semen analysis should repeat at least once;
Methods to monitor ovulation
监测排卵的方法
? Luteinizing Hormone monitoring,
LH surge;
after 34-36 hr occur ovulation;
? Basal Body Temperature,
simple,cheap,biphasic pattern;
? Mid-luteal serum progesterone,> 3ng/mL,peak;
? Premenstrual molimina,95% presence;
? Mucus change,thick and cellular,no crystalline fern;
? Ultrasound monitoring,
follicle size 21-23 mm,fluid in the cul-de-sac.
Treatment principle for
female factors
Causes Treatment
induction of ovulation；
tuboplasty,
microsurgery；
medication or surgery；
immune inhibition；
anovulation
Tubal factor
Anatomic factor
immunologic
azoospermia
genetic disease
after surgery
Failure above
Assisted Reproductive Technologies
(ART) 辅助生育技术unexplained
Induction of ovulation
诱发排卵 -1
1,Clomiphen 氯米芬,ER binding GnRH,FSH/LH
dosage,50 mg,period day 5th,5 days；
2,Gonadotropin therapy 促性腺激素治疗：
Indications,Hypogonadotropic hypogonadism;
Pituitary dysfunction;
COH in IVF;
(COH, controlled ovarian hyperstimulation)
HMG,human menopausal gonadotropins;
FSH 75 IU/LH 75 IU,IM or SC;
Recombinant FSH,75 IU,SC;
3,HCG 绒毛膜促性腺腺激素, 5000-10000 IU;
Induction of ovulation
诱发排卵 -2
4,Gonadotropin releasing hormone agonist
(GnRH-a),hypothalamic factor,as COH;
protocol,according the every GnRH-a
component and feature,the time of
start and discontinuation are different;
zoladex; decapeptyl,dipherenline,
enantone;
5,GnRH antagonist;
6,Bromocriptine 溴隐停, high PRL;
Assisted Reproductive
Technologies (ART) 辅助生育技术
? Intrauterine insemination ( IUI);
宫腔内人工授精 ;
? In vitro fertilization and embryo transfer
(IVF-ET); 体外受精与胚胎移植 ;
? Intracytoplasmic sperm injection (ICSI);
单精子卵泡浆注射；
? Gamete intrafallopian transfer (GIFT);
配子输卵管移植 ;
Intrauterine insemination
( IUI) 人工授精
? Indications:
1,as treatment of male factor infertility;
2,psychological factors;
3,unexplained infertility;
4,genetic defects;
? Types:
1,artificial insemination with husband’s sperm (AIH);
2,artificial insemination by donor (AID);
? Method:
placement of about 0.3 ml of washed,processed
and concentrated sperm into the intrauterine cavity
by trans-cervical catheterizaion.
In vitro fertilization and embryo
transfer (IVF-ET) 体外受精与胚胎移植
? Indications:
1,tubal factor;
2,endometriosis;
3,unexplained infertility;
4,IUI failure;
5,Immunologic factors;
? Method:
1,Superovulation,COH,GnRH-a/FSH(HMG)/HCG;
2,Aspiration of eggs;
3,Fertilization with capacitated sperm;
4,Culture of fertilized egg in the lab;
5,Replacement of fertilized egg into the uterus;
Gamete intrafallopian
transfer (GIFT) 配子输卵管移植
? Indications:
1,unexplained infertility;
2,endometriosis;
3,IUI failure;
4,Premature ovarian failure (POF);
5,Immunologic factors;
? Method:
1,Superovulation is induced as IVF-ET;
2,HCG injection is given;
3,Follicle are aspirated via laparoscopy;
4,Sperm mixed with egg;
5,Replacement of fertilized egg into fallopian tube;
ART Complications
辅助生育技术并发症
? Multiple gestations 多胎妊娠 ;
? Pre-eclampsia 产前子痫 ;
? Ovarian hyperstimulation syndrome (OHSS)
卵巢过激综合征 ;
? Premature birth 早产 ;
? Low birth weight 出生低体重 ;
? Long term emotional,social and psychological
impact 长期影响（情绪，社会，精神） ;
复习思考题
? 1,不孕症应如何进行诊断 ；
? 2,女性不孕的特殊检查有哪些；
习题练习
1,WHO 有关原发不孕症的定义哪个是正确的？
A,性生活正常，未避孕，结婚 3年未孕；
B,性生活正常，未避孕，结婚 2年未孕；
C,性生活正常，避孕，结婚 1年未孕；
D,性生活正常，未避孕，结婚 1年未孕；
E,性生活异常，未避孕，结婚 2年未孕；
习题练习
2,下列有关精液检查哪个是错误的？
A,精液量 3 mL；
B,PH 7.2；
C.室温下 40 分钟液化；
D,精子浓度 5.5X107；
E,精子畸形率 10%；
习题练习
3,28岁，已婚，结婚 2年未孕；月经规则，经期
腹痛 5年，男方体健。妇科检查：子宫大小正
常，后倾，不活动，压痛，双侧附件可触及
6cm囊块； BBT 双相，根据上述症状体征，
考虑不孕的原因是：
A,慢性盆腔炎；
B,结核性盆腔炎；
C,子宫内膜异位症；
D,卵巢癌；
E,输卵管积水；
习题练习
4,32岁，已婚，结婚 2年未孕；月经周期规则，但
间隔时间短，要检查黄体功能异常，下列哪项对
诊断无帮助：
A,诊断性刮宫（月经前）；
B,BBT 测定；
C,血雌激素水平测定；
D,血孕激素测定；
E,血 LH水平测定；
习题练习
5,28岁，已婚，结婚 8年,G3P0,不孕 2年；慢性下
腹痛 4年；月经规则，经量正常，男方体健。妇科
检查：子宫大小正常，双侧附件增厚；内分泌检
查在正常范围，根据上述症状体征，首先进行的
不孕的检查是：
A,BBT；
B,诊断性刮宫 ；
C,宫腔镜；
D,腹腔镜；
E,子宫输卵管碘油造影；
