1. 정의
불임증이란 피임을 하지 않고 정상적인 부부생활을 하면서 일정기간(보통 만 1년)이 경과하여도 임신이 되지 않는 경우를 말하며, 그 중 과거에 한 번도 임신을 해본 적이 없는 경우를 원발성(原發性) 불임이라 하고, 임신 및 분만 경험이 있는 사람이 2년이상 경과해도 불임인 경우를 속발성(續發性) 불임이라 한다.
2. 병인
1. 한방적 원인
(1) 신허(腎虛)
- 先天稟賦不足, 腎氣不足, 後天房勞多産, 命門火衰, 子宮衰弱.
체질이 허약하거나 신장의 기운이 부족한데 무리한 성생활로 인하여 호르몬이 많이 소모되고 양기가 손상되어 충맥과 임맥의 기가 약해져 자궁이 쇠약해짐으로써 임신이 안되는 경우
(2) 간기울결(肝氣鬱結)
- 情志不暢, 肝氣鬱結, 疏泄失常, 氣血不和, 衝任不能相資.
마음이 편하지 않아 간의 기가 울결되어 기운과 피가 조화를 이루지 못하여 충맥과 임맥이 서로 돕지 못하게 됨으로써 임신이 안되는 경우
(3) 담습(痰濕)
- 多由體質肥滿, 痰濕內生, 氣機不暢, 衝任受阻.
평소에 체형이 뚱뚱하여 담과 습이 체내에서 생기게 되면 기가 잘 소통되지 못하여 자궁의 맥이 막혀서 임신이 안되는 경우
(4) 혈허(血虛)
- 多由素體羸弱 或 失血過多 或脾胃兩虛 以致陰虛血少 衝任虧損.
체질이 허약하며 피와 호르몬이 부족하거나 혹은 피를 많이 쏟은일이 있어 음기를 상하여 충맥과 임맥이 허약해짐으로써 임신이 안되는 경우
(5) 자궁한(子宮寒)
- 經期當風受寒, 客于胞中, 或因眞陽不足, 命門火衰不能化氣行水, 寒濕注于胞中, 以致宮寒不孕.
월경중에 바람을 몹시 쐬었다든지 찬 기운이 있는 곳에 오래 머물게 되면 자궁으로 바람기운이나 찬 기운이 들어가서 생기거나 혹은 양기가 부족하여 혈액 순환이 잘 되지 못하고 있을 때 찬 기운과 습한 기운이 자궁에 머물러 임신이 안되는 경우
2. 양방적 원인
(1) 자궁경부인자
- 점액의 양이 적거나 질이 나쁜 경우
- 경관염이 있는 경우
- 산성점액인 경우
(2)자궁인자
- 자궁경부 무발육증
- 선천성 자궁기형
- 자궁근종
- 자궁후경증
- 자궁내유착증
- 자궁내막염
(3) 난관 및 복막인자
빈도 : 여성불임 원인의 약 50%
불임유발기전
난관의 손상등으로 난관폐쇄
난관은 소통되더라도 난관점막의 분비기능, 섬모운동 또는 난관 근육 수축 작용에 이상 발생
(4) 난소인자
배란장애의 원인
① 중추신경계질환 : 종양이나 반흔, 시상하부의 유전적 결손, 정신적 혹은 약물의 영향, 뇌하수체 기능장애나 종양 등에 의한 파괴성 질환
② 중간성 인자 : 영양결핍, 대사성이나 신장, 내분비 혹은 간질환
③ 생식선 인자 : 조기폐경, 난소종양, 난소의 자가면역질환 등에 의한 파괴성 질환 등
(5) 면역학적 인자
자궁경관점액에서의 항정자항체 발견
3. 진단
1. 변증에 의한 약물치료
(1) 신허(腎虛)로 인한 불임
-증상: 월경량이 적으며, 얼굴색은 까칠하고 검은 빛이 돌며 정신도 피로한다. 허리가 아프고 다리에 기운이 없으며 성욕도 줄어들고 소변이 맑게 나오며 대하의 색깔이 묽어진다
-치료법: 신장기능을 돕고 피를 늘려 충임맥을 보한다.
-처방: 온신환, 보신종자탕, 오계환
(2) 혈허(血虛)로 인한 불임
-증상: 월경이 몇 달씩 나오지 않거나 월경량이 적고 색이 묽으며, 또는 월경이 그치지 않고 조금씩 일주일 내지 보름씩 나오고, 몸은 허약해 보이고 얼굴에는 화색이 없으며, 어지럽고 눈에 안화가 생기기도 한다. 가슴이 두근거리기도 하고 맥은 아주 가늘고 가라앉은 맥으로 나타난다.
- 치료법: 호르몬과 피를 늘리며 간과 신을 보할 수 있는 치료를 한다.
- 처방: 양정종옥탕, 청혈양음탕, 청골자신탕
(3) 담습(痰濕)으로 인한 불임
-증상: 월경이 불순하고 색도 흐리며 몸이 뚱뚱하고 얼굴색은 부은 것 같이 희고, 어지러우며 심장이 두근거리기도 한다. 냉은 끈적한 것이 많고 입에서는 묽은 가래가 많이 나오며 명치끝이 더부룩하고 기분이 좋지 않으며 혀에는 흰 설태가 낀다.
- 치료법: 비위기능을 도화 몸의 습과 담을 제거한다.
- 처방: 계궁환
(4) 간울(肝鬱)로 인한 불임
-증상: 월경의 주기가 빨라졌다 느려졌다 불규칙하게 되며 월경량도 적고 월경 전에는 유방이 딱딱하고 팽창하며 월경중에 배가 몹시 아프고, 월경주기가 되면 가슴과 옆구리가 더부룩하고 아프며 기분도 좋지 않아 신경질이 잘 나고 평소에 손끝과 발끝이 차다.
- 치료법: 간의 울기를 풀어 주면서 피를 늘려주고 기운을 소통시키는 치료를 한다.
- 처방: 소요산
(5) 子宮寒으로 인한 불임
-증상: 월경주기가 늦어지고 양도 적으며 혹시 나와도 시원치 못하고 색깔이 자주색을 띠며 덩어리가 있고 월경통이 생기며 아랫배도 차갑다. 맥도 아주 느리고 가라앉은 맥이 나타난다.
- 치료법: 자궁을 덥혀 찬 기운을 풀어주며 월경을 바로 잡아주는 치료를 한다.
- 처방: 애부난궁환
2. 기타 치료법
침치료로는 약침치료와 이침치료, He-Ne Lazer 치료 등이 실시된다. 약침치료는 약의 효과와 침의 효과가 결합된 새로운 형태의 침치료법으로 두침요법의 이론에 따른 두부혈위, 관원혈, 담수, 삼초수 혈위 등을 선택한다. 이침요법은 내분비, 자궁, 난소, 뇌점 등을 자극하여 그 효과를 지속시키는 역할을 한다. 최근에 사용되고 있는 He-Ne Lazer 치료는 혈관의 노폐물을 제거하고 혈액순환을 원활하게 해준다는 실험보고가 있다.
뜸치료로는 세신, 천초 분말을 이용하고 생강편을 그 위에 올린 뒤, 신궐혈에 뜸을 뜨는 방법을 사용하는데 이는 복강내의 순환혈액량을 증가시키고 따뜻하게 해주어 임신에 큰 도움이 되고 있다.
2008년 7월 7일 월요일
2008년 6월 6일 금요일
신촌 이미지 한의원 02-336-7100 불임영어자료
Chapter 10
Infertility
- Definition -
① Sterility : have some absolute factor preventing conception or impregnation,
even with Tx., with the implication that the condition is irreversible.
② Infertility : inability to achieve pregnancy within a stipulated period of time,
usually 1 yrs, or repeated failure to carry a pregnancy to term.
③ Fecundity : childbearing ability
④ Fertility : childbearing performance
⑤ primary infertility : term used to designate those couples who have never conceived
⑥ secondary infertility : indicates that at least one conception has occured for one or
both , but that the couple is currently not able to achieve preg.
- Medical Considerations -
* As the husband or wife, or both, may have factors contribuing to the infertility,
both must cooperate in the investigation. Although the woman is often the most interested
and aggresive in her desire for medical help, it is rarely satisfactory to initiate
an infertility investigation without the husband's cooperation.
1) Goals of an infertility evaluation
① to establish the etiology of infertility
② to give a prognosis for future fertility
⑴ three major areas must be considered in establishing the Dx. & Px.
- Basic Infertility Evaluation -
① age of the wife
② duration of the history
; unprotected intercourse를 1년동안 했음에도 불구하고 임신되지 않으면,
evaluation을 실시해야 한다.
③ medical factors responsible
; detail Hx,P/E,Pevic Exam이 필수적이다.
a) central or ovulation
b) male factor
c) mucus or cervical factor
d) endometrial or uterine factor
e) tubal factor
f) peritoneal factor
* a),b) 는 prognostic Ix of the seriousness of the problem
2) Initial interview
① past and present medical history
② social histroy of the couple
③ establish the motivation and interest of a couple
④ any previous infertility evalutaion
⑤ P/E ( to seeks ovarian or hormaonal dysfunction and physical or mechanical
problems within the pelvis )
3) Fundamental areas of investigation
⑴ central or ovulatory factor
( involving the physical act of ovulation and release of a mature oocyte )
; ovulation의 이상은 menstrual cycles과 관계있고, endocrinologic workup을 실시
⑵ male factor
( involving adequate production of normal sperm )
; STD는 epididymitis, blocked sperm ducts, varicocele, hormonal imbalance,
systemic ds,를 유발하여 sperm production에 이상을 초래할 수 있다.
⑶ mucus or cervical factor
( involving the presence of adequate cervical mucus which can act as a transport
medium and repository for sperm )
; ① mucus quantity → after cervical conization, endocervical gl.가 파괴되었을 때.
② mucus quality → infection , inadequate estrogen stimulation
③ mucus hostility → presence of antisperm antibody
⑷ endometrial or uterine factor
( involving the preparation of the endometrial implantation site that is dependent
on ovarian endocrine function and uterine end-organ normality and response )
; polyps , submucous myomas
⑸ tubal factor
( involving patency of tubes allowing transport of sperm and oocytes )
; end result of infection ( most frequent )
⑹ peritoneal factor
( involving the absence of any physical or mechanical barrier to fertility within
the peritoneal cavity )
; endometriosis , pelvic adhesion
- Infertility Evalution -
1) Central or ovulatory factor
- Diagnosis of ovulation -
Conclusive Pregnancy
Recovery of oocyte from tubal flushing
Recovery of oocyte or embryo from uterine flushing
Observation of ovulation via laparoscopy
Presumptive Biphasic basal temperature
Vaginal cytology
Vaginal pH
Cervical mucus change
Endometrial biopsy
Plasma progesterone
Urinary pregesterone
Plasma 17α-hydroxyprogesterone
Plasma estradiol
LH surge
Salivary glucose
Salivary esterase
Alkaline phosphatase
Premenstrual molimina
Regular cycles
Follicular collapse on U/S
Cul-de-sac fluid on U/S
Corpus luteum visualization via U/S , laparoscopy
- The most helpful change predictive of impedencing ovulation
→ cervical mucosal change under the influence of estrogen
: mucus ↑ in amount, fern formation(+)
→ under the influence of progesterone in the luteal phase
: mucus ↓ in amount, changes in character, fern formation(-)
- luteinized unruptured follicle(LUF) syndrome
→ because of failure of formation of the stigma
→ folliculogenesis and corpus luteum formation : nl
→ endocrine dynamics : nl
→ trapped within the follicle which does not rupture
→ 매우 드물기 때문에 presumptive criteria of ovulation가 유용하다.
- D/Dx of amenorrhea
① hypothalamic amenorrhea → excessive exercise,thinness,stress
② pituitary amenorrhea → prolactin-producing adenoma,panhypopituitarism
③ metabolic & endocrine ds → thyroid dysfunction
④ obesity and hyperandrogenism
⑤ polycystic ovarian, follicular exhaustion, premature menopause
- Treatment
① etiologic diagnosis : first step
② antiestrogen clomiphene citrate
→ correct dysfunction of feedback control mechanisms in pts
with an intact pituitary gland and normal ovaries
③ ② + hCG → cumulative 95% probability of ovulation
④ hMGs or pituitary gonadotropins → 99.9%
2) Male factor
⑴ initial assessment
- Semen analysis
① at least two times
② in the laboratory within 1 hr
③ prewarming the jar to body temperature
④ after a period of abstinence not less than 48 hrs
⑤ by induced ejaculation or by intercourse with withdrawal
- Criteria for a Normal Semen Anaysis -
① Count per mililiter
normal fertile : > 20 million
subfertile : 5 < count < 20
infertile : < 5
② Volume : 2.5 ml
③ Motility : 60% motile within 4 hr of collection
motility ↑ → fertility ↑
④ Differential : less than 25% abnormal forms
- survival time of sperm in the human female genital tract : 96 hrs
sperm can fertilize : 24-48 hrs
- freshly ejaculated spermatozoa는 oocyte를 둘러싼 cellular layers를 통과하지 못한다.
sperm이 ability to fertilize를 갖는 과정을 capitation이라한다.
- capitation
① occurs in the female reproductive tract
② removal of epididymal and seminal plasma proteins coating the sperm surface
③ acrosomal reaction ; activation of hydrolytic enz.(hyaluronidase in acrosome)
and acrosin
allow spermatozoa to digest the cumulus oophorus, the corona radiata,
the zona pellucida of the oocyte
allow fusion of the sperm with the vitelline menmbrane,the inner surface
of zona
⑵ semen abnormalities
* semen analysis → quantity and quality of the spermatozoa
secretory function of the accessory genital glands
등의 정보를 제공.
① seminal insufficiency (due to)
- defect in spermatogenesis, in sperm maturation,
- an abnormality in the components or constituents of the seminal ejaculate
② seminal plasma
- prostate(30%) + seminal vesicles(60%) + epididymis,ampullae,bulbourethral,
urethral gl (5-10%)
③ pH of seminal plasma ( normal semen = pH 7.2 -7.8 )
- prostatic fluid ; acidic and inhibitory to sperm → acid phosphatase
- vesicular secretion ; alkaline → fructose and prostaglandins
ex) acute or chronic vesiculitis, high fructolysis, androgen deficiency
→ low fructose levels → dysfuction of seminal vesicles
⑶ evaluation of the infertile male
- History
① cryptorchism,scrotal trauma,torsion
② recurrent episodes of prostatis,epididymitis,urethritis
③ occupational & environmental exposures to radiation,toxins,chemicals,pesticides
④ nonspecific factors : stress,anxiety,travel
⑤ over-the-counter medications taken,drug,alcohol use,abuse
⑥ potency,sexual techniques,frequency of intercourse
- Constitutional factors
① nutritional problem,acute or chronic illness,general metabolic ds
② Klinfelter's syndrome
③ Kartagener's syndrome
④ varicocele
- Drug history
① phenothiazine → retrograde ejaculation
② cardiovascular drug (adrenergic inhibitor,antihypertensives) → ejaculatory disturbance
③ furadantin → necrospermia
④ sulfasalazine → inhibits spermatogenesis
⑤ colchicine → transient inhibition of spermatogenesis,azoospermia
- P/E
① androgenization ( gynecomastia,beard & chest↓,eunuchoid proportions )
② intact sense of smell looks for a rare form of hypogonadism,Kallmann's syndrome
③ bimanual scrotal palpation ( testicular size,spermatocele,absent vas deference )
④ phimosis,meatal stenosis,hypospadias
⑤ valsalva maneuver ( varicocele )
- Laboratory evaluation of oligospermic male
⒜ pregerminal hypofertility
→ FSH(nl) , better prognosis
→ Tx : tamoxifen,clomiophene citrate,menopausal or chorionic gonadotropin,testosterone
⒝ primary germinal hypofertility
→ FSH(↑) , tubular damage , exogenous hormonal stimulation은 효과 없다.
⒞ postgerminal hypofertility
→ FSH(nl) ,anatomic obstruction of the reproductive tract,
history of infection(gonorrhea,epididymitis)
contrast vasography : preoperative diagnosis를 confirm하기위해
testicular biopsy
- Classification of Male infertility -
Ⅰ. Pretesticular or Pregerminal Causes
; oligospermia, azoospermia, FSH↓, LH↓, testosterone↓
Ⅱ. Testicular Causes
; azoospermia, oligospermia, FSH↑, LH & testosterone nl or ↓
Ⅲ. Posttesticular Causes
; azoospermia, FSH nl , LH & testosterone nl
- Penetration test
① Kremer test ( sperm-cervical mucus contact test,SCMCT )
→ phalanx formation가 즉시 일어나고,sperm이 mucus를 통과한다.(normal)
→ shivering-shaking phenomenon시에는 antisperm antibody test를 실시해야함.
② Sperm penetration assay(SPA) or cross-species penetration test
→ ability of sperm to penetrate an oocyte
-
abnormal inconclusive normal
semen analysis semen analysis semen anaysis
↓ ↓ ↓ ↓ ↓
repeat ↓ repeat ↓ ↓
↓ ↓ ↓ ↓ ↓
abnormal ↓ inclusive ↓ ↓
↓ ↓ ↓ ↓ ↓
↓ ↓
↓ sperm penetration assay ↓
↓ ↓
↓ ↑ 14-100% ↓
≤10%
male infertility ← → female infertility
evaluation evaluation
- Cause of Male Infertility -
Ⅰ. Pretesticular or Pregerminal Causes
Ａ. Central Gonadotropin Deficiensy
Hypothalamic → congenital GnRH deficiensy, tumor, infection, head trauma
Pituitary → congenital FSH/LH deficiency, tumor, infarction ,
infection, trauma
Other → sarcoidosis, hemachromatosis
Ｂ. Endocine Excess Syndrome
Estrogen → functional tumor of adrenal , cirrhosis
Androgen → congenital adrenal hyperplasia, androgen-producing tumor
Glucocorticoid → cushing's synd, steroid tx.( ulcerative colitis,asthma )
Ｃ. Other
Hypothyroidism , DM
Ⅱ. Testicular Causes
Ａ. Chromosomal abnormalities → Klinefelter' synd , 47-XXY
Ｂ. Cryptochidism,unilateral or bilateral
Ｃ. Radiation , chemotherapy
Ｄ. Mumps , viral orchitis
Ｅ. Trauma
Ｆ. Sertoli-cell-only synd
Ｇ. Idiopathic maturation arrest
Ｈ. Androgen receptor abnormality → androgen insensitivity synd
Ⅲ. Posttesticular Causes
Ａ. Congenital ductal obstruction → vas deferens , epididymis
Ｂ. Acquired ductal block → infection ( gonorrhea,Tbc ) , vas ligation
Ｃ. Impaired motility → Kartagener's synd , Immotile cilia synd ,
Enz. deficiency ( protein carboxymethylase )
- Treatment
① low dose testosterone → to increase sperm motility
② Cup insemination technique in wife → low semen volume with good quality sperm일때
③ split ejaculation → high semen vol일때,
→ artificial insemination using the initial part of ejaculation
→ concentrate sperm without the dilutional effect
④ intrauterine insemination → mucus hostility or absence일때
⑤ competent sexual therapist → impotence and psychosexual difficulty
⑥ therapy of varicocele
→ high ligation of the internal spermatic vein
→ HCG therapy after ligation
⑦ low dose continuous or cyclic clomiphene citrate → FSH,LH↑
→ men with pregerminal causes of oligospermia 에 유용
→ Cx : visual scotoma
⑧ tamoxiphen (estrogen antagonist similar to clomiphene but without its estrgen effect)
⑨ retrograde ejaculation시 ← sympathomimetic medication
⑩ dilute alkaline urine → sperm survival chance ↑
ⓐ limitation of smoking,excessive alcohol intake,attention to diet,adequate rest,
treatment of any chronic illness or metabolic disease
⑷ technique of insemination
a) Homologous Artificial Insemination (AIH)
< Indication >
① when potentially normal semen does not reach the cervix
→ hypospdias,spinal cord injury,psychogenic impotence,vaginismus,
local or anatomical problem
② retrograde ejaculation
→ after transurethral prostatectomy,in DM,
→ during phenothiazine(Thorazine,Mellaril) treatment,
catheterization of the bladder or postcoital voiding
③ impotence,premature ejaculation,anatomical abnormalities
b) Therapeutic Donor Insemination (TDI,AID)
< Selection of donor >
① proven fertility,healthy,physically fit,emotionally stable,intelligent,
free of any familial history of congenital,hereditary defects
② resemble the patient's husband in somatic type,hair,eye color
③ his blood type should be compatible with the wife
④ no history of vereneal disease,drug abuse,significant alcohol intake
< Donor screening >
; syphilis,hepatitis B,HIV,blood group,Rh,Tay-Sachs,Sickle cell anemia,thalassemia,
occupation,religion,ancestry
< Several rules of thumb >
① husband must have aware of his inadequacy
② husband has taken the initiative
③ no religious background in either partner
④ every reasonable medical investigation and aid must have been employed
to diagnosis and treat the cause of male infertility
⑤ normal fertility in the female ( The wife must be immune to rubella )
< Timing of insemination >
→ in the periovulatory
→ monitoring : history,BBt,cervical mucus evaluation,
use of Ovusticks(to indicate the timing of the LH surge),U/S
< Method >
① cervical cup,usually → vagina의 acid한 상태를 거치지 않으므로 sperm이 오래 생존.
② cervico-vaginal
③ fresh semen → usually used,but on occasion a frozen donor specimen is utilized
④ twice a cycle
** mixed the husband's sperm with that of the donor
→sperm agglutination between specimens
** intercourse prior to insemination or after the cup has been removed
→ more practice
c) Intrauterine Insemination
< Indication >
① male factor infertility → oligospermia,poor motility
② cervical factor infertility
→ hostility,antisperm Ab,inadequate or infected mucus,unexplained infertility,
conization pts without cervical mucus
< S/E >
; allergic rxn,fever,cramping,sever dysmenorrhea(PG와 연관),infection
< Method >
① direct transfer of sperm to the intrauterine cavity
② using a washed and concentrated specimen(PG 제거)
③ by using an angiocath,pediatric feeding tube,epidural cather
3) Cervical factor
- Cervical mucus function
① sperm penetrability
② sperm nutrition
③ sperm reservoir and survival
- Examination of the cervical mucus
① amount
② quality(viscosity,spinnbarkeit,crystallization,epithelial cell,bacteria),
③ presence or absence of infection
- Good estrogenic mucus
① in the preovulatory and periovulatory phase
② watery,copious,clear
③ acellular
④ excellent spinnbarkit ( 8cm or longer )
⑤ supoport motility of sperm
⑥ ferning
- Low estrogenic mucus
① in the luteal phase under progesterone influence
② in the postmenstrual phase
③ scanty,thick,cloudy
④ highly cellular
⑤ not ferning
⑥ not support sperm penetration
- Postcoital test ( PCT,Sims-Huhner test )
< Method >
① at periovulatory phase
② when the cervical mucus is well estrogenized
③ intercourse within 12-42 hrs of her visit
④ Tuberculin syringe
⑤ successful test → at least 5-10 actively motile sperm/HPF
< Normal PCT > implies
① satisfactory intercourse techniques
② normal mucus for the transport and preservation of sperm
③ adequate ovarian estrogenic function
④ at least the possibility of normal male fertility
→ one negative PCT has little clinical value and must be repeated.
< Abnormal PCT >
① inadequate amount of cervical mucus
# Cause → stenosis of endocervical canal,congenital
→ inadequate numbers or response of endocervical gl.
; secondary to acute or chronic cervitis or to conization
or cryosurgical therapy
# Treatment → low dose estrogen therapy
; ethinyl estradiol(EE2,10ug) or diethystilbestrol(DES,0.1mg)
→ daily from days 3 to 14 of the 28-day cycle
→ higher estrogen dose for a shorter time
; higher estrogen dose for a shorter time
→ EE2 ( 200ug daily for 5 days from day 8-12 of the cycle )
→ hMG(Pergonal) stimulation → endogenous estrogen output
② abnormal or hostile cervical mucus
; abnormal mucus quality usually implies an infected mucus.
# infected mucus ← vibramycin(100mg) for 10 days,from the 1st day of menses
# Chlamydia trachomatis,mycoplasma in the cevix → not related to infertility
# Chlamydial salpingitis → significant etiologic cause of infertility
# Chlamydia in the cervix ← tetracycline
③ faulty coital technique,oligospermia,lack of semen volume,vaginal factor,
poor sperm motility, sperm immobilization
④ failure of penetration of sperm into the cervical mucus
→ d/t a thick abnormal mucus or acrosomal defect in the sperm
⑴ antisperm antibodies
- sperm agglutinating activity in the cervical mucus → nonselective & nonspecific
- immobilization Ab : IgG,IgM,specific for sperm-coating proteins or acrosomeor midpiece
protein, complemen-dependent,correlate with female infertility
- secretory IgA → local Ab,capable of embryo toxicity
① Isojima sperm immobilization test
→ clinically reliable
→ its sensitivity has been increased by using washed spermatozoa
& an adequate amount of complement
→ test performed on the serum of husband and wife
② Gelatin agglutination test ( Kibrick method )
③ Tube-slide agglutination test ( Frankin-Dukes methods )
④ Sperm cervical mucus contact test,SCMCT ( Kremer test )
→ important screening test for the presence of antisperm Ab within cervical mucus
⑤ Slide test → sperm,mucus cross match test
⑵ treatment of immunologic infertility
① washing and concentration of sperm with intracervical or intrauterine insemination
② high dose steroid therapy as an immunosuppressant
→ methylprednisolone 32mg 3 days daily for 10 days.
starting at the wife's cycle day 21
→ agitation,emotional problem,bilateral aseptic necrosis of femoral head
③ condom contrception for 3 months
→ E.coli 에 의해 infection됬을때 reproductive tract에서 Ab가 형성되고, 이 Ab가
sperm과 cross-reaction한다.condom이 E.coli Ab형성을 감소시킨다.
4) Endometrial or uterine factor
# study of Premenstrual endometrium → information about ovarian luteal function and
the implantation site for the fertilized ovum.
# Endometrial biopsy
- with a Novak currete
- from high in the fundus
- according to the menstrual history & BBT chart
- within 1-2 days of menstruation
- Accurate endometrial dating by the criteria of Noyes et al is most satisfactory just
prior to the onset of menses and the biopsy serves as a bioassay of corpus luteum
progesterone output.
⑴ luteal phase inadequacy
< Definition >
- the histologic dating of the endometrium is 2 or more days behind the menstrual
dating in 2 or more cycles
- defective follicular development and inappropriate endometrial development
< Etiology >
a) insufficient progesterone exposure or inappropriate progesterone-estrogen ratio
→ defective progesterone output
- during the first ovulatory cycles following delivery or abortion
- in the over 35 year old woman
- in athletes undergoing strenuous training programs
- hyperprolactinemia
- unexplained infertility
- clomiphene-induced ovulations
b) inappropriately responded endometrium
→ inadequate numbers of endometrial progesterone cytosel receptors
< Clinical entities >
- early recurrent miscarriage
- primary infertility
- submucosal miscarrige
< Diagnosis >
- late luteal endometrial biopsy
- BBT
- serum prolactin , TSH ↓
- sge & nutritional status of the patient
< Treatment >
① correction of nutritional deficiencies,hypothyroidism,hyperprolactinemia
② progesterone vaginal suppositories
- 25mg twice daily
- begining 3 or 4 days into the luteal phase
- counting until the onset of menses
③ progesterone 12.5mg IM daily
④ hCG 2500IU daily
- luteotropic hormone
- stimulate the normal corpus luteum to synthesize an increased amount of progesterone
- unpredictable
< Ix of progesterone supplementation >
① regulatory ovulatory woman
② with cycle length less than 40 days
③ no another cause such as hyperprolactinemia,or hypothyroidism
④ under the age of 35
⑤ normal uterine cavity on hysterosalpingogram
< Prolonged follicular phase >
① d/t inadequacy of the intercycle FSH increase
② administration of clomiphene of gonadotropin
< Synthetic progestational agents >
- cIx in pregnancy
- ineffective → the effect on the endometrium is not equivalent to that of progesterone
- luteolytic effect → decreased progesterone output
⑵ Endometritis
- plasma cell → pathognomic
- lymphocytes & macrophages → ureaplasma endometritis
- doxycycline 200mg on the first day
100mg daily for 10 days
5) Tubal factor
- tubal function test → diagnostic & therapeutic
⑴ gas insufflation ( Rubin's test )
⑵ hysterosalpingography ( HSG )
< Time >
- after menstrual bleeding has ceased and prior to ovulation
→ radioresistant oocyte in prophase of meiosis I
< Finding >
- a collection of contrast → hydrosalpinx or peritubal adhesion
- nonvisualization of tubes → cornual obstruction or spasm
( atropin 0.5mg,glucagon 1mg IV )
< Oil-soluble media >
# disadvantage
; oil embolus,granuloma formation,remain longer in the pelvis
# advantage → water-soluble media 보다 좋다.
; greater therapeutic,
the incidence of conception increases during the 3-4 months after HSG,
clear image,
less pain with peritoneal spill
** The possibility of infection after HSG ( acute PID )
- patent dilated tubes on HSG
- doxycycline prophylaxis
6) Peritoneal factor
⑴ Definition
; those physical or mechanical barriers to infertility occuring within the pelvis
→ peritubal adhesions, endometriosis
⑵ Diagnosis
; diagnostic laparoscopy with instillation of indigo carmine or methylene blue dye
through the tubes
⑶ Tubal or Fimbrial occlusion
; result of adhesion from PID due to gonorrhea,Tbc,postabortal or postpartum infection
⑷ Adhesions
→ d/t endometriosis
→ other irritating reactions in the peritoneal cavity
( unrecognized ectopic pregnancy,ruptured corpus luteum cyst,bleeding from
the follicle at ovulation )
→ previous pelvis surgery ( ovarian wedge resection )
→ extrapelvic inflammation process
( regional enteritis,appendiceal abscess,IUD )
⑸ Treatment
① HSG → diagnosis & rupture minor adhesion
② lysis of adhesion,by laparoscopy or laparotomy
③ linear salpingostomy for removal of ectopic pregnancy
④ tuboplasty
- corneal implantation
- fimbrioplasty → delay in conception
- resection → anastomosis
⑤ prevention of peritoneal adhesion formation postoperatively
- high molecular weight dextran intraperitoneally
- hydrotubation with solutions of cortisone & antibiotics
7) Unexplained infertility
- fewer than 5% of infertile couples
- doxycycline treatment
- Other Consideration -
1) Psychogenic aspects of infertility
→ emotional tension
frustration tubal spasm
anger ovulatory defects
guilt decreased coital frequency
isolation pychogenic impotence
ejaculatory problem
infertility ←
- In Vitro Fertilization -
1) indications for IVF
① irreparably damaged or missing fallopian tubes
② abnormal cervical factor
③ oligospermia & male factor
④ immunologic infertility
⑤ unexplained infertility
⑥ endometriosis
⑦ EDS exposure
⑧ significant fimbrial disease
2) patient selection
; patient's age , weight , method used to aspirate oocytes 에 따라 성공률이 달라진다.
3) ovulation timing
; most important step of the process of IVF is to stimulate follicular development
and oocyte maturation.
; daily monitoring using serum estradiol and follicular diameter with U/S
; ovulation will occur over 36 hrs after the administration of IM hCG
; oocyte aspiration is timed to occur before spontaneous ovulation can happen.
4) stimulation protocols
- hMG alone
- hMG + clomophene
- hMG + pure FSH
- GnRH
5) aspiration of oocytes
- laparoscopy under local or general anesthesia
- transabdominal transvesicle U/S-guided approach
- transvaginal U/S-guided technique
6) fertilization in Vitro
⑴ Grading system for oocyte maturity
① size & expansion of the cumulus
② appearance of the corona radiata & ooplasm
③ the degree of darkness of the granulosa cells
⑵ Insemination
- 6-24 hrs later
⑶ Fertilization
- within 15-18 hrs of insemination
7) embryo transfer
- 2-8 cell stage
- 48-60 hrs after insemination
8) success of IVF/ET
⑴ Pregnancy rate
- transfer of one embryo, 10-15%
- transfer of two embryo, 20-25%
- 3 or more embryo, 30%
⑵ Multiple gestation → common
- Gamete Intrafallopian Transfer (GIFT) -
; The placement of gametes,sperm & oocytes,into the fallopian tube
through the laparoscopy or via a minilaparotomy
- 4 oocytes are removed from patient
- 2 per side or a total of 4 oocytes plus sperm are introduced into the tubes
- no incubation & culture procedures
- Nonsurgical Ovum Transfer -
⑴ Method
- wife : completely inaccesible ovary
- The donor is inseminated in a normal ovulatory cycle
- 4-5 days later,by uterine flushing technique
recovering the fertilized oocyte,now an embryo at the blastocyst stage.
- with proper synchronization,transfer of the embryo at the wife
with the hope of intrauterine pregnancy
⑵ Complication
- oocyte donor → the possibility of intrauterine or ectopic pregnancy and infection
Infertility
- Definition -
① Sterility : have some absolute factor preventing conception or impregnation,
even with Tx., with the implication that the condition is irreversible.
② Infertility : inability to achieve pregnancy within a stipulated period of time,
usually 1 yrs, or repeated failure to carry a pregnancy to term.
③ Fecundity : childbearing ability
④ Fertility : childbearing performance
⑤ primary infertility : term used to designate those couples who have never conceived
⑥ secondary infertility : indicates that at least one conception has occured for one or
both , but that the couple is currently not able to achieve preg.
- Medical Considerations -
* As the husband or wife, or both, may have factors contribuing to the infertility,
both must cooperate in the investigation. Although the woman is often the most interested
and aggresive in her desire for medical help, it is rarely satisfactory to initiate
an infertility investigation without the husband's cooperation.
1) Goals of an infertility evaluation
① to establish the etiology of infertility
② to give a prognosis for future fertility
⑴ three major areas must be considered in establishing the Dx. & Px.
- Basic Infertility Evaluation -
① age of the wife
② duration of the history
; unprotected intercourse를 1년동안 했음에도 불구하고 임신되지 않으면,
evaluation을 실시해야 한다.
③ medical factors responsible
; detail Hx,P/E,Pevic Exam이 필수적이다.
a) central or ovulation
b) male factor
c) mucus or cervical factor
d) endometrial or uterine factor
e) tubal factor
f) peritoneal factor
* a),b) 는 prognostic Ix of the seriousness of the problem
2) Initial interview
① past and present medical history
② social histroy of the couple
③ establish the motivation and interest of a couple
④ any previous infertility evalutaion
⑤ P/E ( to seeks ovarian or hormaonal dysfunction and physical or mechanical
problems within the pelvis )
3) Fundamental areas of investigation
⑴ central or ovulatory factor
( involving the physical act of ovulation and release of a mature oocyte )
; ovulation의 이상은 menstrual cycles과 관계있고, endocrinologic workup을 실시
⑵ male factor
( involving adequate production of normal sperm )
; STD는 epididymitis, blocked sperm ducts, varicocele, hormonal imbalance,
systemic ds,를 유발하여 sperm production에 이상을 초래할 수 있다.
⑶ mucus or cervical factor
( involving the presence of adequate cervical mucus which can act as a transport
medium and repository for sperm )
; ① mucus quantity → after cervical conization, endocervical gl.가 파괴되었을 때.
② mucus quality → infection , inadequate estrogen stimulation
③ mucus hostility → presence of antisperm antibody
⑷ endometrial or uterine factor
( involving the preparation of the endometrial implantation site that is dependent
on ovarian endocrine function and uterine end-organ normality and response )
; polyps , submucous myomas
⑸ tubal factor
( involving patency of tubes allowing transport of sperm and oocytes )
; end result of infection ( most frequent )
⑹ peritoneal factor
( involving the absence of any physical or mechanical barrier to fertility within
the peritoneal cavity )
; endometriosis , pelvic adhesion
- Infertility Evalution -
1) Central or ovulatory factor
- Diagnosis of ovulation -
Conclusive Pregnancy
Recovery of oocyte from tubal flushing
Recovery of oocyte or embryo from uterine flushing
Observation of ovulation via laparoscopy
Presumptive Biphasic basal temperature
Vaginal cytology
Vaginal pH
Cervical mucus change
Endometrial biopsy
Plasma progesterone
Urinary pregesterone
Plasma 17α-hydroxyprogesterone
Plasma estradiol
LH surge
Salivary glucose
Salivary esterase
Alkaline phosphatase
Premenstrual molimina
Regular cycles
Follicular collapse on U/S
Cul-de-sac fluid on U/S
Corpus luteum visualization via U/S , laparoscopy
- The most helpful change predictive of impedencing ovulation
→ cervical mucosal change under the influence of estrogen
: mucus ↑ in amount, fern formation(+)
→ under the influence of progesterone in the luteal phase
: mucus ↓ in amount, changes in character, fern formation(-)
- luteinized unruptured follicle(LUF) syndrome
→ because of failure of formation of the stigma
→ folliculogenesis and corpus luteum formation : nl
→ endocrine dynamics : nl
→ trapped within the follicle which does not rupture
→ 매우 드물기 때문에 presumptive criteria of ovulation가 유용하다.
- D/Dx of amenorrhea
① hypothalamic amenorrhea → excessive exercise,thinness,stress
② pituitary amenorrhea → prolactin-producing adenoma,panhypopituitarism
③ metabolic & endocrine ds → thyroid dysfunction
④ obesity and hyperandrogenism
⑤ polycystic ovarian, follicular exhaustion, premature menopause
- Treatment
① etiologic diagnosis : first step
② antiestrogen clomiphene citrate
→ correct dysfunction of feedback control mechanisms in pts
with an intact pituitary gland and normal ovaries
③ ② + hCG → cumulative 95% probability of ovulation
④ hMGs or pituitary gonadotropins → 99.9%
2) Male factor
⑴ initial assessment
- Semen analysis
① at least two times
② in the laboratory within 1 hr
③ prewarming the jar to body temperature
④ after a period of abstinence not less than 48 hrs
⑤ by induced ejaculation or by intercourse with withdrawal
- Criteria for a Normal Semen Anaysis -
① Count per mililiter
normal fertile : > 20 million
subfertile : 5 < count < 20
infertile : < 5
② Volume : 2.5 ml
③ Motility : 60% motile within 4 hr of collection
motility ↑ → fertility ↑
④ Differential : less than 25% abnormal forms
- survival time of sperm in the human female genital tract : 96 hrs
sperm can fertilize : 24-48 hrs
- freshly ejaculated spermatozoa는 oocyte를 둘러싼 cellular layers를 통과하지 못한다.
sperm이 ability to fertilize를 갖는 과정을 capitation이라한다.
- capitation
① occurs in the female reproductive tract
② removal of epididymal and seminal plasma proteins coating the sperm surface
③ acrosomal reaction ; activation of hydrolytic enz.(hyaluronidase in acrosome)
and acrosin
allow spermatozoa to digest the cumulus oophorus, the corona radiata,
the zona pellucida of the oocyte
allow fusion of the sperm with the vitelline menmbrane,the inner surface
of zona
⑵ semen abnormalities
* semen analysis → quantity and quality of the spermatozoa
secretory function of the accessory genital glands
등의 정보를 제공.
① seminal insufficiency (due to)
- defect in spermatogenesis, in sperm maturation,
- an abnormality in the components or constituents of the seminal ejaculate
② seminal plasma
- prostate(30%) + seminal vesicles(60%) + epididymis,ampullae,bulbourethral,
urethral gl (5-10%)
③ pH of seminal plasma ( normal semen = pH 7.2 -7.8 )
- prostatic fluid ; acidic and inhibitory to sperm → acid phosphatase
- vesicular secretion ; alkaline → fructose and prostaglandins
ex) acute or chronic vesiculitis, high fructolysis, androgen deficiency
→ low fructose levels → dysfuction of seminal vesicles
⑶ evaluation of the infertile male
- History
① cryptorchism,scrotal trauma,torsion
② recurrent episodes of prostatis,epididymitis,urethritis
③ occupational & environmental exposures to radiation,toxins,chemicals,pesticides
④ nonspecific factors : stress,anxiety,travel
⑤ over-the-counter medications taken,drug,alcohol use,abuse
⑥ potency,sexual techniques,frequency of intercourse
- Constitutional factors
① nutritional problem,acute or chronic illness,general metabolic ds
② Klinfelter's syndrome
③ Kartagener's syndrome
④ varicocele
- Drug history
① phenothiazine → retrograde ejaculation
② cardiovascular drug (adrenergic inhibitor,antihypertensives) → ejaculatory disturbance
③ furadantin → necrospermia
④ sulfasalazine → inhibits spermatogenesis
⑤ colchicine → transient inhibition of spermatogenesis,azoospermia
- P/E
① androgenization ( gynecomastia,beard & chest↓,eunuchoid proportions )
② intact sense of smell looks for a rare form of hypogonadism,Kallmann's syndrome
③ bimanual scrotal palpation ( testicular size,spermatocele,absent vas deference )
④ phimosis,meatal stenosis,hypospadias
⑤ valsalva maneuver ( varicocele )
- Laboratory evaluation of oligospermic male
⒜ pregerminal hypofertility
→ FSH(nl) , better prognosis
→ Tx : tamoxifen,clomiophene citrate,menopausal or chorionic gonadotropin,testosterone
⒝ primary germinal hypofertility
→ FSH(↑) , tubular damage , exogenous hormonal stimulation은 효과 없다.
⒞ postgerminal hypofertility
→ FSH(nl) ,anatomic obstruction of the reproductive tract,
history of infection(gonorrhea,epididymitis)
contrast vasography : preoperative diagnosis를 confirm하기위해
testicular biopsy
- Classification of Male infertility -
Ⅰ. Pretesticular or Pregerminal Causes
; oligospermia, azoospermia, FSH↓, LH↓, testosterone↓
Ⅱ. Testicular Causes
; azoospermia, oligospermia, FSH↑, LH & testosterone nl or ↓
Ⅲ. Posttesticular Causes
; azoospermia, FSH nl , LH & testosterone nl
- Penetration test
① Kremer test ( sperm-cervical mucus contact test,SCMCT )
→ phalanx formation가 즉시 일어나고,sperm이 mucus를 통과한다.(normal)
→ shivering-shaking phenomenon시에는 antisperm antibody test를 실시해야함.
② Sperm penetration assay(SPA) or cross-species penetration test
→ ability of sperm to penetrate an oocyte
-
abnormal inconclusive normal
semen analysis semen analysis semen anaysis
↓ ↓ ↓ ↓ ↓
repeat ↓ repeat ↓ ↓
↓ ↓ ↓ ↓ ↓
abnormal ↓ inclusive ↓ ↓
↓ ↓ ↓ ↓ ↓
↓ ↓
↓ sperm penetration assay ↓
↓ ↓
↓ ↑ 14-100% ↓
≤10%
male infertility ← → female infertility
evaluation evaluation
- Cause of Male Infertility -
Ⅰ. Pretesticular or Pregerminal Causes
Ａ. Central Gonadotropin Deficiensy
Hypothalamic → congenital GnRH deficiensy, tumor, infection, head trauma
Pituitary → congenital FSH/LH deficiency, tumor, infarction ,
infection, trauma
Other → sarcoidosis, hemachromatosis
Ｂ. Endocine Excess Syndrome
Estrogen → functional tumor of adrenal , cirrhosis
Androgen → congenital adrenal hyperplasia, androgen-producing tumor
Glucocorticoid → cushing's synd, steroid tx.( ulcerative colitis,asthma )
Ｃ. Other
Hypothyroidism , DM
Ⅱ. Testicular Causes
Ａ. Chromosomal abnormalities → Klinefelter' synd , 47-XXY
Ｂ. Cryptochidism,unilateral or bilateral
Ｃ. Radiation , chemotherapy
Ｄ. Mumps , viral orchitis
Ｅ. Trauma
Ｆ. Sertoli-cell-only synd
Ｇ. Idiopathic maturation arrest
Ｈ. Androgen receptor abnormality → androgen insensitivity synd
Ⅲ. Posttesticular Causes
Ａ. Congenital ductal obstruction → vas deferens , epididymis
Ｂ. Acquired ductal block → infection ( gonorrhea,Tbc ) , vas ligation
Ｃ. Impaired motility → Kartagener's synd , Immotile cilia synd ,
Enz. deficiency ( protein carboxymethylase )
- Treatment
① low dose testosterone → to increase sperm motility
② Cup insemination technique in wife → low semen volume with good quality sperm일때
③ split ejaculation → high semen vol일때,
→ artificial insemination using the initial part of ejaculation
→ concentrate sperm without the dilutional effect
④ intrauterine insemination → mucus hostility or absence일때
⑤ competent sexual therapist → impotence and psychosexual difficulty
⑥ therapy of varicocele
→ high ligation of the internal spermatic vein
→ HCG therapy after ligation
⑦ low dose continuous or cyclic clomiphene citrate → FSH,LH↑
→ men with pregerminal causes of oligospermia 에 유용
→ Cx : visual scotoma
⑧ tamoxiphen (estrogen antagonist similar to clomiphene but without its estrgen effect)
⑨ retrograde ejaculation시 ← sympathomimetic medication
⑩ dilute alkaline urine → sperm survival chance ↑
ⓐ limitation of smoking,excessive alcohol intake,attention to diet,adequate rest,
treatment of any chronic illness or metabolic disease
⑷ technique of insemination
a) Homologous Artificial Insemination (AIH)
< Indication >
① when potentially normal semen does not reach the cervix
→ hypospdias,spinal cord injury,psychogenic impotence,vaginismus,
local or anatomical problem
② retrograde ejaculation
→ after transurethral prostatectomy,in DM,
→ during phenothiazine(Thorazine,Mellaril) treatment,
catheterization of the bladder or postcoital voiding
③ impotence,premature ejaculation,anatomical abnormalities
b) Therapeutic Donor Insemination (TDI,AID)
< Selection of donor >
① proven fertility,healthy,physically fit,emotionally stable,intelligent,
free of any familial history of congenital,hereditary defects
② resemble the patient's husband in somatic type,hair,eye color
③ his blood type should be compatible with the wife
④ no history of vereneal disease,drug abuse,significant alcohol intake
< Donor screening >
; syphilis,hepatitis B,HIV,blood group,Rh,Tay-Sachs,Sickle cell anemia,thalassemia,
occupation,religion,ancestry
< Several rules of thumb >
① husband must have aware of his inadequacy
② husband has taken the initiative
③ no religious background in either partner
④ every reasonable medical investigation and aid must have been employed
to diagnosis and treat the cause of male infertility
⑤ normal fertility in the female ( The wife must be immune to rubella )
< Timing of insemination >
→ in the periovulatory
→ monitoring : history,BBt,cervical mucus evaluation,
use of Ovusticks(to indicate the timing of the LH surge),U/S
< Method >
① cervical cup,usually → vagina의 acid한 상태를 거치지 않으므로 sperm이 오래 생존.
② cervico-vaginal
③ fresh semen → usually used,but on occasion a frozen donor specimen is utilized
④ twice a cycle
** mixed the husband's sperm with that of the donor
→sperm agglutination between specimens
** intercourse prior to insemination or after the cup has been removed
→ more practice
c) Intrauterine Insemination
< Indication >
① male factor infertility → oligospermia,poor motility
② cervical factor infertility
→ hostility,antisperm Ab,inadequate or infected mucus,unexplained infertility,
conization pts without cervical mucus
< S/E >
; allergic rxn,fever,cramping,sever dysmenorrhea(PG와 연관),infection
< Method >
① direct transfer of sperm to the intrauterine cavity
② using a washed and concentrated specimen(PG 제거)
③ by using an angiocath,pediatric feeding tube,epidural cather
3) Cervical factor
- Cervical mucus function
① sperm penetrability
② sperm nutrition
③ sperm reservoir and survival
- Examination of the cervical mucus
① amount
② quality(viscosity,spinnbarkeit,crystallization,epithelial cell,bacteria),
③ presence or absence of infection
- Good estrogenic mucus
① in the preovulatory and periovulatory phase
② watery,copious,clear
③ acellular
④ excellent spinnbarkit ( 8cm or longer )
⑤ supoport motility of sperm
⑥ ferning
- Low estrogenic mucus
① in the luteal phase under progesterone influence
② in the postmenstrual phase
③ scanty,thick,cloudy
④ highly cellular
⑤ not ferning
⑥ not support sperm penetration
- Postcoital test ( PCT,Sims-Huhner test )
< Method >
① at periovulatory phase
② when the cervical mucus is well estrogenized
③ intercourse within 12-42 hrs of her visit
④ Tuberculin syringe
⑤ successful test → at least 5-10 actively motile sperm/HPF
< Normal PCT > implies
① satisfactory intercourse techniques
② normal mucus for the transport and preservation of sperm
③ adequate ovarian estrogenic function
④ at least the possibility of normal male fertility
→ one negative PCT has little clinical value and must be repeated.
< Abnormal PCT >
① inadequate amount of cervical mucus
# Cause → stenosis of endocervical canal,congenital
→ inadequate numbers or response of endocervical gl.
; secondary to acute or chronic cervitis or to conization
or cryosurgical therapy
# Treatment → low dose estrogen therapy
; ethinyl estradiol(EE2,10ug) or diethystilbestrol(DES,0.1mg)
→ daily from days 3 to 14 of the 28-day cycle
→ higher estrogen dose for a shorter time
; higher estrogen dose for a shorter time
→ EE2 ( 200ug daily for 5 days from day 8-12 of the cycle )
→ hMG(Pergonal) stimulation → endogenous estrogen output
② abnormal or hostile cervical mucus
; abnormal mucus quality usually implies an infected mucus.
# infected mucus ← vibramycin(100mg) for 10 days,from the 1st day of menses
# Chlamydia trachomatis,mycoplasma in the cevix → not related to infertility
# Chlamydial salpingitis → significant etiologic cause of infertility
# Chlamydia in the cervix ← tetracycline
③ faulty coital technique,oligospermia,lack of semen volume,vaginal factor,
poor sperm motility, sperm immobilization
④ failure of penetration of sperm into the cervical mucus
→ d/t a thick abnormal mucus or acrosomal defect in the sperm
⑴ antisperm antibodies
- sperm agglutinating activity in the cervical mucus → nonselective & nonspecific
- immobilization Ab : IgG,IgM,specific for sperm-coating proteins or acrosomeor midpiece
protein, complemen-dependent,correlate with female infertility
- secretory IgA → local Ab,capable of embryo toxicity
① Isojima sperm immobilization test
→ clinically reliable
→ its sensitivity has been increased by using washed spermatozoa
& an adequate amount of complement
→ test performed on the serum of husband and wife
② Gelatin agglutination test ( Kibrick method )
③ Tube-slide agglutination test ( Frankin-Dukes methods )
④ Sperm cervical mucus contact test,SCMCT ( Kremer test )
→ important screening test for the presence of antisperm Ab within cervical mucus
⑤ Slide test → sperm,mucus cross match test
⑵ treatment of immunologic infertility
① washing and concentration of sperm with intracervical or intrauterine insemination
② high dose steroid therapy as an immunosuppressant
→ methylprednisolone 32mg 3 days daily for 10 days.
starting at the wife's cycle day 21
→ agitation,emotional problem,bilateral aseptic necrosis of femoral head
③ condom contrception for 3 months
→ E.coli 에 의해 infection됬을때 reproductive tract에서 Ab가 형성되고, 이 Ab가
sperm과 cross-reaction한다.condom이 E.coli Ab형성을 감소시킨다.
4) Endometrial or uterine factor
# study of Premenstrual endometrium → information about ovarian luteal function and
the implantation site for the fertilized ovum.
# Endometrial biopsy
- with a Novak currete
- from high in the fundus
- according to the menstrual history & BBT chart
- within 1-2 days of menstruation
- Accurate endometrial dating by the criteria of Noyes et al is most satisfactory just
prior to the onset of menses and the biopsy serves as a bioassay of corpus luteum
progesterone output.
⑴ luteal phase inadequacy
< Definition >
- the histologic dating of the endometrium is 2 or more days behind the menstrual
dating in 2 or more cycles
- defective follicular development and inappropriate endometrial development
< Etiology >
a) insufficient progesterone exposure or inappropriate progesterone-estrogen ratio
→ defective progesterone output
- during the first ovulatory cycles following delivery or abortion
- in the over 35 year old woman
- in athletes undergoing strenuous training programs
- hyperprolactinemia
- unexplained infertility
- clomiphene-induced ovulations
b) inappropriately responded endometrium
→ inadequate numbers of endometrial progesterone cytosel receptors
< Clinical entities >
- early recurrent miscarriage
- primary infertility
- submucosal miscarrige
< Diagnosis >
- late luteal endometrial biopsy
- BBT
- serum prolactin , TSH ↓
- sge & nutritional status of the patient
< Treatment >
① correction of nutritional deficiencies,hypothyroidism,hyperprolactinemia
② progesterone vaginal suppositories
- 25mg twice daily
- begining 3 or 4 days into the luteal phase
- counting until the onset of menses
③ progesterone 12.5mg IM daily
④ hCG 2500IU daily
- luteotropic hormone
- stimulate the normal corpus luteum to synthesize an increased amount of progesterone
- unpredictable
< Ix of progesterone supplementation >
① regulatory ovulatory woman
② with cycle length less than 40 days
③ no another cause such as hyperprolactinemia,or hypothyroidism
④ under the age of 35
⑤ normal uterine cavity on hysterosalpingogram
< Prolonged follicular phase >
① d/t inadequacy of the intercycle FSH increase
② administration of clomiphene of gonadotropin
< Synthetic progestational agents >
- cIx in pregnancy
- ineffective → the effect on the endometrium is not equivalent to that of progesterone
- luteolytic effect → decreased progesterone output
⑵ Endometritis
- plasma cell → pathognomic
- lymphocytes & macrophages → ureaplasma endometritis
- doxycycline 200mg on the first day
100mg daily for 10 days
5) Tubal factor
- tubal function test → diagnostic & therapeutic
⑴ gas insufflation ( Rubin's test )
⑵ hysterosalpingography ( HSG )
< Time >
- after menstrual bleeding has ceased and prior to ovulation
→ radioresistant oocyte in prophase of meiosis I
< Finding >
- a collection of contrast → hydrosalpinx or peritubal adhesion
- nonvisualization of tubes → cornual obstruction or spasm
( atropin 0.5mg,glucagon 1mg IV )
< Oil-soluble media >
# disadvantage
; oil embolus,granuloma formation,remain longer in the pelvis
# advantage → water-soluble media 보다 좋다.
; greater therapeutic,
the incidence of conception increases during the 3-4 months after HSG,
clear image,
less pain with peritoneal spill
** The possibility of infection after HSG ( acute PID )
- patent dilated tubes on HSG
- doxycycline prophylaxis
6) Peritoneal factor
⑴ Definition
; those physical or mechanical barriers to infertility occuring within the pelvis
→ peritubal adhesions, endometriosis
⑵ Diagnosis
; diagnostic laparoscopy with instillation of indigo carmine or methylene blue dye
through the tubes
⑶ Tubal or Fimbrial occlusion
; result of adhesion from PID due to gonorrhea,Tbc,postabortal or postpartum infection
⑷ Adhesions
→ d/t endometriosis
→ other irritating reactions in the peritoneal cavity
( unrecognized ectopic pregnancy,ruptured corpus luteum cyst,bleeding from
the follicle at ovulation )
→ previous pelvis surgery ( ovarian wedge resection )
→ extrapelvic inflammation process
( regional enteritis,appendiceal abscess,IUD )
⑸ Treatment
① HSG → diagnosis & rupture minor adhesion
② lysis of adhesion,by laparoscopy or laparotomy
③ linear salpingostomy for removal of ectopic pregnancy
④ tuboplasty
- corneal implantation
- fimbrioplasty → delay in conception
- resection → anastomosis
⑤ prevention of peritoneal adhesion formation postoperatively
- high molecular weight dextran intraperitoneally
- hydrotubation with solutions of cortisone & antibiotics
7) Unexplained infertility
- fewer than 5% of infertile couples
- doxycycline treatment
- Other Consideration -
1) Psychogenic aspects of infertility
→ emotional tension
frustration tubal spasm
anger ovulatory defects
guilt decreased coital frequency
isolation pychogenic impotence
ejaculatory problem
infertility ←
- In Vitro Fertilization -
1) indications for IVF
① irreparably damaged or missing fallopian tubes
② abnormal cervical factor
③ oligospermia & male factor
④ immunologic infertility
⑤ unexplained infertility
⑥ endometriosis
⑦ EDS exposure
⑧ significant fimbrial disease
2) patient selection
; patient's age , weight , method used to aspirate oocytes 에 따라 성공률이 달라진다.
3) ovulation timing
; most important step of the process of IVF is to stimulate follicular development
and oocyte maturation.
; daily monitoring using serum estradiol and follicular diameter with U/S
; ovulation will occur over 36 hrs after the administration of IM hCG
; oocyte aspiration is timed to occur before spontaneous ovulation can happen.
4) stimulation protocols
- hMG alone
- hMG + clomophene
- hMG + pure FSH
- GnRH
5) aspiration of oocytes
- laparoscopy under local or general anesthesia
- transabdominal transvesicle U/S-guided approach
- transvaginal U/S-guided technique
6) fertilization in Vitro
⑴ Grading system for oocyte maturity
① size & expansion of the cumulus
② appearance of the corona radiata & ooplasm
③ the degree of darkness of the granulosa cells
⑵ Insemination
- 6-24 hrs later
⑶ Fertilization
- within 15-18 hrs of insemination
7) embryo transfer
- 2-8 cell stage
- 48-60 hrs after insemination
8) success of IVF/ET
⑴ Pregnancy rate
- transfer of one embryo, 10-15%
- transfer of two embryo, 20-25%
- 3 or more embryo, 30%
⑵ Multiple gestation → common
- Gamete Intrafallopian Transfer (GIFT) -
; The placement of gametes,sperm & oocytes,into the fallopian tube
through the laparoscopy or via a minilaparotomy
- 4 oocytes are removed from patient
- 2 per side or a total of 4 oocytes plus sperm are introduced into the tubes
- no incubation & culture procedures
- Nonsurgical Ovum Transfer -
⑴ Method
- wife : completely inaccesible ovary
- The donor is inseminated in a normal ovulatory cycle
- 4-5 days later,by uterine flushing technique
recovering the fertilized oocyte,now an embryo at the blastocyst stage.
- with proper synchronization,transfer of the embryo at the wife
with the hope of intrauterine pregnancy
⑵ Complication
- oocyte donor → the possibility of intrauterine or ectopic pregnancy and infection
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