1. Human Reproductive Disorder
Xulan
Dept. of G & O, the First Affiliated Hospital of Shantou University Medical College

2. Introduction of Infertility
※ Definition
Fecund: the ability to reproduce, typically used in context of women to become pregnant.
Infertility: the inability to conceive after two years or more of trying with unprotected intercourse for couples.
( WHO, one year)

3. Primary infertility: no previous pregnancies have occurred
Secondary infertility: a prior pregnancy has occurred, but inability to conceive again for two or more years exposure to intercourse, no matter how the result of the pregnancy is.

4. What are the chances of a fertile couple actively seeking pregnant in a single month or cycle? 10%-20%
The accumulated pregnancy rate during two years
__chances of conceiving by 6 months: 75%
__chances of conceiving by 1 year:90%
__10%-15%of couples will require longer than one year to conceive.

5. Epidemiology and etiology of infertility
Causes Percentage
Female factors %
Male factors %
Both male and
female factors %
unexplained factors %
So, the initial evaluation should include both the partners.

6. ※ Female Infertility
Causes
Ovulatory dysfunction: 25%.
Tubal factors: 30%-50%
3. Pelvic factors
4. Cervical factors
5. Extra-genital tract factors
6. Others

7. Female Factors Follopian tube Uterine ovary oocyte Cervix
Hypothalamus
Pituitary
Follopian tube
Uterine
ovary oocyte
Cervix
Extra-genital tract
Fig.1sperm
Thyroid
Adrenal

8. Ovulatory dysfunction
1. Hypothalamus: amenarrhea or mensrtual disorder
-- Emotional depress
-- Psychological trauma
-- Environmental and Climate changes
2. Pituitary diseases：
--Sheehan’s syndrome
-- Pituitary tumor: Hyperprolactinemia,
-- Empty sella syndrome

9. Ovary diseases:
1. Congenital dysformation:
Turner’s syndrome(45,XO)
2. Polycystic syndrom(PCO)
3. Premature ovary failure(POF)
4. Ovary functional tumors
5. Insensitive to follicle stimulating hormones(FSH).
6. Other endocrinologic diseases: adrenal or thyroid dysfunction

11. ● Pelvic Factors
Tubal factors: tubal blokage, adhension and hydrosalpinx
1. Inflammations
--Chlamydia
--Gonorrhea
--Tubercle bacillus and so on
2. Tubal dysformation
3. Pelvic adhension: endometriosis
4. Abdominal or pelvic surgery
5. Ectopic pregnancy

12. Fig.2

13. ●Pelvic factors
Pelvic Adhension
1.Inflammations:
--Chlamydia, turbercle bacillum, gonorrhea, staphylococci and so on
2. Pelvic endometriosis
3. Pelvic surgery
●Reproductive system dysformation
-- Mayer-Rokitansky- Kuster-Hauser syndrome: no uterus and vagina

14. -- Uterus didelphys
-- Uterus bicornis
-- Uterus septus
-- Uterus unicornis
-- Rudimentary horn of uterus
-- others

15. Fig.3

16. Fig.4

17. Fig.5

18. Fig.6

19. Fig.7

20. Fig.8

21. Fig.9

22. Fig.10

23. Fig.11

24. Fig.12

25. Fig.13-1
Fig.13-2

26. Cervical factors
-- Cervicitis :
cervical erosion,
cervical polyps,
cervical hyperplasia
-- cervical stenosis
-- Cervical tumors: leiomyoma
-- Cervical cancer

27. ●Extra-genital factors
-- Vulvo-vaginalitis
-- Vulvo-tumors
● Others
--Immunological factors:
autoimmune response;
auto-antibodies: AsAb, ACA, ANA, etc.
-- Genetic factors
-- Psychological factors:
-- Unexplained causes

28. Evaluation and diagnosis
Initial evaluation
The initial visit is the most important; the infertility is a problem of both of the couple; so, the male partner should be present at the beginning.

29. 1. Taking history:
-- marriage, menarche, menstruation
-- duration of sexual relationships with or without birth control
-- methods of birth control
-- reproductive history of both partners (ie: children with previous partners/marriages)

30. 2. Physical examination (PE)
--General development
-- Secondary sexual characteristics
3. Pelvic examination (PV)
-- Bimanual exam
-- Rectal-vaginal exam

31. 4. Breast exam: masses and galactorrhea
5. Laboratory:
-- hormonal testing:
-- urinary LH surge test
-- vaginal shedding cells test
-- cervical mucus test
-- post-coital sperm—cervical mucus test
6. Assisted imaging examination
-- Ultrasound B continuous monitoring
-- HSG
-- Hysteroscopy
-- Laparoscopy

32. Treatment for female fertility
General therapy
-- Watchful waiting (provide more time for unassisted conception)
-- more frequent intercourse at mid-cycle
-- emotional support

33. 2. Special therapy
-- treatment of pelvic inflammation disease（PID）
-- hydrotubation:
-- selective salpingogram and recanalization: to make the obstructed site of the tube reopen under X-ray guidance
-- hysteroscopy：removal of submucous leiomyoma, endometrial polyps, complete or incomplete uterus septum and separation of the cavity adhension.
-- laparoscopy: adhension separation, ovarian tumors and leiomyoma removal

34. Surgical approaches:
-- ovary cysts and tumors
-- severe pelvic adhension
-- Leiomyomas out of uterus wall
Physical treatment for cervical erosion:
-- laser light
-- crpyotherapy
-- electrotherapy
Anti-tuberculosis:
-- endometrial tuberculosis
-- salpingotuberculosis.

35. Medication therapy
Ovulation induction
Clomiphene citrate(CC)
M mg qn×5
2. CC/HMG/HCG
M5-9 CC mg
M10-11 HMG 75IU qd
3. LHRH pulsive therapy
4. Bromocriptine---hyperprolactinemia
5. Metformin---PCO

36. 6. HMG/HCG
M3 HMG 75IU qd
F 18-25mm, EN 8-10mm
HCG10000IU qd
● Progesterone supplement
1. Post-ovulation, progesterone 10-20mg
qd×7-10 days
2. HCG 2000IU-5000IUq3d82
3. Low dosage thyroid 20mg qd
● Assisted reproductive technology （not discussed here)

37. Methods to monitor ovulation
-- Luteinizing Hormone monitoring:
LH surge-- ovulation occurs after hr,
BBT--simple, cheap, biphasic pattern,
-- Mid-luteal serum progesterone: > 15.7nmol/mL, peak;
-- Premenstrual molimina: 95% presence,
-- Mucus change: thick and cellular, no crystalline fern,
-- Ultrasound monitoring: follicle size mm,
fluid in the cul-de-sac.

38. ※ Male infertility
Causes
1. PRE-TESTICULAR CAUSES OF INFERTILITY
a. Hypothalamic disease 
Isolated gonadotropin deficiency (Kallmann's syndrome) 
Isolated LH deficiency ("Fertile eunuch") 
Isolated FSH deficiency Congenital hypogonadrotropic syndromes

39. b. Pituitary disease 
Pituitary insufficiency (tumors, infiltrative processes, operation, radiation) 
Hyperprolactinemia 
Hemochromatosis 
Exogenous hormones (estrogen-androgen excess, glucocorticoid excess, hyper and hypothyroidism).

40. 2. TESTICULAR CAUSES OF INFERTILITY
Chromosomal abnormalities: Klinefelter's syndrome (XXY, karayotype), XX disorder (sex reversal syndrome), XYY syndrome
Noonan's syndrome (male Turner's syndrome)
Myotonic dystrophy- Bilateral anorchia (vanishing testes syndrome)
Sertoli-cell-only syndrome (germinal cell aplasia)

41. Gonadotoxins (drugs, radiation)
Orchitis
Trauma
Systemic disease (renal failure, hepatic disease, sickle cell disease)
Defective androgen synthesis or action
Cryptorchidism
Varicocele

42. 3. POST-TESTICULAR CAUSES OF INFERTILITY ● Congenital disorders
a. Disorders of sperm transport 
● Congenital disorders 
● Acquired disorders 
● Functional disorders
b. Disorders of sperm motility or function 
● Congenital defects of the sperm tail 
● Maturation defects 
● Immunologic disorders 
● Infection
3. Sexual dysfunction

43. Fig.14

44. Fig.15

45. Fig.16

46. Fig.17

47. ● Evaluation and diagnoses
1.History collection:
-- period of infertility without protected intercourse
-- present and previous marriage,
-- previous fertile history with partners,
-- frequency of intercourse,
-- method of birth control,
-- harmful habits: cigarette, alcohol, drug-injection

48. 2. Physical examination
-- development of body: height and ratio of
upper body sigment to low body sigment
-- Secondary sexual characteristics
Inadequate body hair
atypical genital hair distribution
gynecomastia

49. -- Exam of reproductive system
Size, masses (length, volume and mass) of scrotum
Use orchidometer if possible
Epididymis for scarring ,absence or induration
Vas deferense for absence or nodules
Varicocele
3. Laboratory test
-- Semen analysis
-- Karyotype (chromosome)

50. Normal Values for Semen Analysis
Volume > 2.0 mL
Sperm concentration > 20 million/mL
Motility >50 %
A >25%
A＋B >50%
morphology >30 % normal
Data from WHO, 1992

51. Abnormal Values for Semen Analysis
azoospermia—no sperm found under microscope for at twice SA at two weeks interval
oligospermia—sperm count less than 20 million per 1mL
asthenospermia—the percentage of normal morphology sperm less than 30%

52. -- Endocrine test: <3%
FSH,LH,T,PRL,E2,T3,T4,ACTH,TSH,GH
hyperprolactinemia--MR
-- Blood biochemistry
Liver enzymes and blood lipid
-- Immunologic antibody: AsAb
-- Special and sperm function tests
Sperm-Cervical mucus interaction
Sperm penetration assays
Acrosome evaluation
Hypoosmotis swelling

53. -- Bacteriologic test
Bacterial culture for urine or prostate gland fluid
and drug sensitive test
Chlamydia trachomatis
Mycoplasma hominus
Ureaplasma urealyticulum
● Treatment
1. Surgical measures
-- Varicocelectomy—varicocele
-- Transurethral resection of ejaculatory duct

54. -- Microsurgical epididymal sperm aspiration
-- Ablation of pituitory Adenomas
-- Prophylactic surgical measures—undescended testes
2. Medical measures
--Endocine therapy
HMG,HCG,CC,Bromocriptine
-- Treatment of infection
antibiotics
-- Empiric therapy—herbal treatment
3. Assisted reproductive techniques treatment