Case 1
Patient,Woman,age 19
Complaint,No menstruation by age 19
Present history,General feels good,but has no secondary
sex changes and no periods,No cyclic abdominal pain.
Past history,Nothing special noted.
Case 2
Patient,Woman age 30
Complaint,No menstruation; Hot and sweating.
Present history,Normal menstrual cycle,IUD removal 8
month ago,Amount of bleeding in the following
menstruation was markedly reduced,and there was no
bleeding for the second cycle,She was put on a sequential
therapy with estrogens and progesterone,but no withdrawal
bleeding was noted,Two months ago she started to feel hot
and sweating in particular in the morning and the symptoms
was getting worse.
Past history,Married at age 25,Pregnant 2 months after
marriage,had an artificial abortion at 46 days,An IUD was
inserted then.
Amenorrhea
(闭经）
Definitions
Primary amenorrhea (原发闭经 ):
(1) No periods by age 16
(2) No periods by age 14 with no secondary sex changes
(3) No periods by 2 years after the start of secondary
sex changes
Secondary amenorrhea (继发闭经 ):
Absence of normal menstruation in a patient with
previously established cycles.
(1) At any age when menses have ceased for more
than 6 months or
(2) longer than the total length of three previous
menstrual cycles
1) Infertility (due to anovulation)
2) Osteoporosis and atrophy of the reproductive
tract (due to low level of estrogen)
3) Endometrial cancer
(due to prolonged stimulation by estrogen)
4) Psychological problems in adolescents
Problems associated with amenorrhea
Definitions
Primary amenorrhea
Differentiation of the primitive gonads (原始性腺 )
starts at 6 weeks.
Y chromosome encodes the testis determining factor
(TDF)→formation of testis (睾丸 )
Mesonephric duct/Wolffian duct (中肾管 ) → male
reproductive tract,vas deference (输精管 ),epididymis
(附睾 ),ejaculatory duct (射精管 ) and seminal vesicle
(精囊 )
Paramesonephric duct/Mullerian duct (副中肾管 )
→fallopian tubes,uterus,vagina (upper 1/3)
Primary amenorrhea
Etiology
? Genetic causes
? Developmental abnormality
1,Presence of secondary sex
characteristics
Etiology
1) Mullerian agenesis syndrome
(米勒管发育不全综合征 )
Mayer-Rokitansky-Kuster-Hauser syndrome
(1) Karyotype,46,XX
(2) Normal ovary,fallopian tubes,absence of uterus
and vagina
(3) Normal FSH
(4) Normal secondary sex characteristics
Primary amenorrhea
Primary amenorrhea
Etiology
2) Androgen insensitivity syndrome
(雄激素不敏感综合征 )
Testicular feminization (睾丸女性化 )
(1) Karyotype,46,XY
(2) Presence of testis with normal production of Es & Ts
No androgen receptors in target end-organs
(3) Presence of secondary sex characteristics
(incomplete)
(4) No vagina and uterus
Primary amenorrhea
Etiology
3) Savage syndrome (对抗性卵巢综合征 )
Resistant ovary syndrome (卵巢不敏感综合征 )
(1) Karyotype,46,XX
(2) Presence of ovary with primordial and primary
follicles
(3) No gonadotropin receptors
(4) FSH ↑
(5) Near normal secondary sex characteristics
Etiology
4) Congenital abnormalities in the lower
reproductive tract
(1) Imperforate hymen (处女膜闭锁 )
(2)Transverse vaginal septum (阴道横隔 )
(3)Absence of lower 1/3 vagina
Primary amenorrhea
Etiology
2,Abscence of secondary sex characteristics
1) Hypogonadotropic hypogonadism
(低促性腺激素性性腺功能减退 )
Kallmann’s syndrome (嗅觉缺失综合征）
Congenital absence of GnRH secretion accompanied
by anosmia （ 嗅觉丧失） or hyposmia（ 嗅觉减退）
(1) Karyotype,46,XX
(2) Normal differentiation of internal sex organs
(3) No secondary sex characteristics
Primary amenorrhea
Etiology
2) Hypergonadotropic hypogonadism
(高促性腺激素性性腺功能减退 )
(1) Congenital gonadal dysgenesis (先天性性腺发育不全综
合征）
Turner’s syndrome (特纳综合征 )
Karyotype,45,XO (60%); 45,XO/46,XX; 45,XO/47,
XXX.
FSH&LH ↑Estrogens↓
Manifestations,Female phenotype but poorly developed sex
organs,short stature,webbed neck,mentally retarded
Primary amenorrhea
Etiology
(2) 46,XX pure gonadal dysgenesis
(46,XX单纯性腺发育不全）
Streak gonad (条索状性腺 )
Primary amenorrhea
(3) 46,XY pure gonadal dysgenesis /Swyer syndrome
(46,XY单纯性腺发育不全）
Testis development↓→ Testosterone ↓ & MIF ↓
a) Testosterone ↓ → Development of mesonephric duct ↓
→ Male reproductive tract ↓
b) MIF ↓ → Development of paramesonephric duct
→ Development of female reproductive tract
Manifestations,Female phenotype,gonadotropins ↑&
estrogens ↓,not well-developed sex organs,
streak gonad (条索状性腺 ) containing Leydig cells
Primary amenorrhea
1/3 chromosomal abnormalities
Karyotyping (核型分析 )
46,XY,testicular feminization
pure gonadal dysgenesis
For 46,XX with normal pelvic examination
Progestin withdrawal test and FSH
No bleeding,FSH ↑,Gonadal dysgenesis,ovarian failure
No bleeding,FSH ↓ /→, Hypogonadotripic hypogonadism
Central nervous system tumor or
trauma
Bleeding,Congenital adrenogenital syndrome
Feminizing ovarian tumor
Diagnosis of primary amenorrhea
Diagnosis of primary amenorrhea
Normal breast,normal uterus,Similar to that of secondary
amenorrhea
Normal breast,poor uterus,Testosterone and Karyotyping
46,XX & female level of T,Mullerian dysgenesis
46,XY & male level of T,Androgen insensitivity
Poor breast,poor uterus,Karyotyping
46,XX,Congenital absence of uterus
46,XY,Pure gonadal dysgenesis
Poor breast,normal uterus,Karotyping & FSH
FSH ↑,Gonadal dysgenesis (e.g,Turner’s syndrome)
FSH ↓ /→, Hypothalamus or pituitary gland
Secondary Amenorrhea
Central nervous system
Hypothalamus 55%
Pituitary 20%
Ovary 20%
Uterus 5%
Outflow tract
Menses
GnRH
FSH,LH
Estrogen,progesterone
Etiology and Classification
1,Central nervous system and hypothalamic
Most common,mostly dysfunction
1) Psychogenic (stress)
CRH ?pulsatile GnRH secretion ?
2) Weight loss/Nutritional deprivation
Anorexia nervosa （ 神经性厌食症）
Weight loss ? GnRH concentration ?
3) Strenuous exercise
Reduction in proportion of adipose tissue
GnRH secretion?
Etiology and Classification
4) Drug induced
e.g,oral contraceptives,chlorpromazine (氯丙嗪 ),
reserpin (利血平 )
? GnRH?
? dopamine ? ? Prolactin ?
5) Tumors (Fig2abc)
e.g,craniopharyngioma （ 颅咽管瘤）
that interrupts transfer of GnRH and dopamin
to the pituitary
? gonadotropins ?
? prolactin ?
Etiology and Classification
1) Sheehan’s syndrome (希恩综合征 )
The syndrome results from ischemic necrosis of the
pituitary gland,This is caused by acute thrombosis （ 血
栓形成） of the pituitary blood vessels after profound
hypotension and hypovolemia due to postpartum
bleeding,The production of gonadotrophic,thyrotrophic
and adrenotrophic hormones ceases or is very inadequate.
Hypothyroidism,hypocorticism
2,Pituitary
Etiology and Classification
2) Pituitary tumors (Fig3)
e.g,Prolactinoma （ 垂体泌乳素瘤）,the most
common pituitary tumor
Prolactin ? ? dopamine? ? GnRH?
Prolactin ? ? making ovary less responsive to
gonadotropins
Etiology and Classification
3) Empty sella syndrome(Fig4ab)
Transfer of GnRH and dopamin to the
adenohypophysis is interrupted.
Etiology and Classification
1) Premature ovarian failure
? ≤ 40 years
? Exhaustion of follicles
? Causes,autoimmune factors,oophoritis (卵巢炎 ),
mumps virus,idiopathic,iatrogenic (e.g,surgery,
radiation,chemotherapy)
3,Ovarian
Etiology and Classification
2) Sex hormone secreting ovarian tumors
Sertoli-Leydig cell tumor
(支持细胞－间质细胞肿瘤 /睾丸母细胞瘤 )
Hilus cell tumor (门细胞瘤）
Granulosa or theca cell tumor
(颗粒细胞或卵泡膜细胞瘤 )
Etiology and Classification
3) Polycystic ovarian syndrome (PCOS)
(多囊卵巢综合征 )
LH/FSH↑& Androgens ↑
Manifestations:
Abnormal uterine bleeding amenorhea
Infertility
Hirsutism (多毛症 )
Obesity
Etiology and Classification
1) Asherman’s syndrome (Fig6)
Secondary amenorrhea caused by traumatization
of the endometrium,Vigorous curettage of the
postabortal and postpartum uterus can damage the
basal layer of the endometrium and lead to adhesion,
Tuberculosis and intrauterine infection may also
damage the endometrium causing adhesion.
4,Uterus/Outflow tract
Etiology and Classification
2) Endometritis
3) Hysterectomy or radiation
5,Amenorrhea caused by other endocrine
disorders
Thyroid function
Adrenal function
Etiology and Classification
Diagnosis
? Location of the lesion
? Causes of the amenorrhea.
1,Medical history
2,Physical examination
3,Evaluating components of the menstrual
cycle control mechanism
1) Progestin test
Withdrawal bleeding (＋ ):
Withdrawal bleeding (－ ):
2) E/P sequential test
Withdrawal bleeding (＋ ):
Withdrawal bleeding (－ ):
Evaluation of Uterine Status
Normal uterus
Presence of E
Either absence of E or a
uterine cause
Normal uterus (but low E)
Uterine cause
Further examination of
uterine cavity or the
outflow tract is indicated.
Diagnosis
Evaluation of Ovarian Function
1) BBT
2) Cervical mucus
3) Vaginal smear
(exfoliated cells)
Diphase:
ovulation
Spinbarkeit and fernlike:
estrogen influence
Oval bodies:
progesterone influence
Superficial layer cells:
estrogen influence
Diagnosis
Chang in follicle size (reduction)
or image:
ovulation
Low levels of E and P,
ovarian or pituitary dysfunction
High level of T:
PCOS,etc.
Positive (increase in estrogen):
the lesion at pituitrary or above
Negative (no increase in E):
ovary
4) B ultrasound
monitoring
ovulation
5) Measurement of
serum steroid
hormones
6) Ovary stimulating
test (HMG
stimulating test)
Evaluation of Ovarian Function
Diagnosis
Evaluation of Pituitary and Hypothalamic Function
1) Measurement of serum
PRL,FSH,LH
2) Pituitary stimulating test
(LHRH stimulating test)
PRL>25ug/L:
prolectinemia
FSH>40U/L:
ovarian failure
LH>25U/L:
PCOS
FSH,LH<5U/L:
pituitary or
hypothalamic disorder
Positive:
hyopthalamic disorder
Negative:
pituitary
Diagnosis
Diagnosis
Flow chart of the diagnosis
Simultaneous measurement of steroid
hormones (E,P,T) and gonadotropins (FSH,
LH) and PRL,TSH is more common and
efficient.
Diagnosis
Case 1
Patient,Woman,age 19
Complaint,No menstruation by age 19
Present history,General feels good,but has no secondary
sex changes and no periods,No cyclic abdominal pain.
Past history,Nothing special noted.
Physical examination,breast not well developed
Genitalia not mature
Uterus small
B ultrasound,small uterus,small ovary containing follicles
Karyotype,46,XX
Endocrine,FSH 1.14 U/L,LH 1.6 U/L,
E2 &P low
T & PRL normal
Pituitary stimulation test,30min,60min,
90min,no increase in LH
Case 1
Case 2
Patient,Woman age 30
Complaint,No menstruation; Hot and sweating.
Present history,Normal menstrual cycle,IUD removal 8
month ago,Amount of bleeding in the following
menstruation was markedly reduced,and there was no
bleeding for the second cycle,She was put on a sequential
therapy with estrogens and progesterone,but no withdrawal
bleeding was noted,Two months ago she started to feel hot
and sweating in particular in the morning and the symptoms
was getting worse.
Past history,Married at age 25,Pregnant 2 months after
marriage,had an artificial abortion at 46 days,An IUD was
inserted then.
Physical examination,normal
Ultrasound,normal uterus and small ovaries
Uteroscopy,Adhesions
Endocrine,FSH 63,LH 41
E low
PRL normal
Diagnosis,Ashermann syndrome
Premature ovarian failure
Case 2
Treatment
Choices of treatment depend on causes of amenorrhea,
gonadotropin levels,and desire for childbearing.
1.Medication
1) For amenorrhea due to prolactinoma or hyper-
prolactinemia,
Bromocriptine(溴隐亭 ),dopamin receptor activator
2) For amenorrhea due to hypothyroidism,
Thyroid powder
3) For amenorrhea due to hypergonadotrophic ovarian
dysfunction,
Replacement therapy with E or Sequential E/P
4) For amenorrhea due to hypogonadotrophic amenorrhea,
if childbearing is desired,
Ovulation induction with CC,HMG,GnRHa,HCG;
if childbearing is not desired,
Cyclic progestins.
5) For amenorrhea due to PCOS,
Oral contraceptives
2,Surgical treatment
1) Deformity,imperforate hymen,etc.
2) Asherman sydrome
3) Tumors
Treatment
Infertility (不孕症 )
Infertility
Failure to achieve conception for two years in spite of
normal sexual life.
Primary infertility
No pregnancy has ever been achieved before
Secondary infertility
Failure to achieve conception for two years in spite of
previous successful pregnancies.
According to the WHO criteria,one instead of two years.
Definitions
Etiology
Female,40-55%
Male,25-40%
Both sides,20%
Idiopathic,10%
Female factors
1,Anovulation (25%)
(1) Central nervous system/hypothalamic
(2) Pituitary
(3) Ovarian
(4) Others
2,Tubal (1/3)
(1) Mechanical
(2) Local envrionment
3,Uterine
4,Cervical
5,Vaginal
Etiology
Male factors
1,Abnormal spermatogenesis
2,Abnormal transfer of sperms
3,Sexual dysfunction
4,Immune disorders
Both factors
1,Low quality of semen
2,Immune disorders
3,Anxieties
4,Lack of knowledge
Etiology
Diagnosis
The key point in treating infertility is to identify the causes.
A,Male factors
History of tuberculosis or mumps
Sexual life
Semen analysis
B,Female factors
1,Medical history
2,Physical examination
3,Infertility specific examinations
1) Ovarian function test
2) Tubal patency
3) Pelvis or uterine status
(1) Laparoscopy
(2) B ultrasound
(3) Hysteroscopy
4) Immunological tests
(1) Postcoital test
(2) Cervical mucus and semen fusion test
(3) Detection of antisperm antibody
Diagnosis
Treatment
1.Correction of organic causes
2,Ovulation induction
3,Assisted reproductive technology
1) Intrauterine insemination (IUI) (宫腔内人工授精）
AIH,Artificial insemination with husband’s sperm
AID,Artificial insemination by donor.
2) In vitro fertilization and embryo transfer (IVF-ET)
(体外受精与胚胎移植 )
Indications,
（ meaning,now these conditions can be treated with IVF-ET),
(1) Tubal factor.
(2) Endometriosis that failed conventional therapy,
(3) Cases that failed the ovulation induction and IUI
treatment
(4) Infertility due to unknown factors
(5) Immune infertility
(6) Male factor (男方少弱精）
Treatment
IVF-ET
Procedures:
1,Controlled ovarian hyperstimulation
2,Oocyte retrieval
3,In vitro fertilization
4,Embryo culture and transfer
5,Luteal support
6,Pregnancy test
Treatment
IVF-ET
Controlled ovarian hyperstimulation
Treatment
Controlled ovarian hyperstimulation
Treatment
Oocyte retrieval
Treatment
In vitro fertilization
Treatment
Eight cell embryo
Treatment
Intracytoplasmic sperm injection (ICSI)
（ 卵泡浆单精子注射）
What will be the future of IVF-ET?
The Wonder of Life
Medical problems
sword with two edges,ICSI
Social,legal problems
Biological parents
marriage between sister and brothers
Ethics problems
But the same is true for the other diseases,
esp,hereditary diseases,cancer (should be a young
cancer patient be treated and given the opportunity
to produce offsprings and then leaving higher risk of
getting cancer to their children?,
Diabetes,hypertension,
What will be human like in future?
In the long long run,
human will lose their ability to produce offsprings
naturally,because selection process by the nature
has been avoided,Without selection,human being will
physically become weaker and weaker,
victums of modern civilization
