武功密笈

小黃藏書

1. Definitions:

¬ Infertility: 1 year of unprotected intercourse without pregnancy

¬ Primary Infertility: infertility in which no previous pregnancies have occurred

¬ Secondary Infertility: infertility in which a prior pregnancy, although not

necessarily a live birth, has occurred

¬ Fecundability: the probability of achieving pregnancy within a single menstrual

cycle

¬ Fecundity: the probability of achieving a live birth within a single cycle

　

2. Causes of Infertility:

– Age:

• An association between the age of the woman and reduced fecundability has been well documented
• The age-related decline in fertility appears to be attributable to oocyte depletion.
• The older age is also associated with increased risk of spontaneous abortion.

– Abnormalities in the semen (male factor infertility):

• Prevalence: 25-40 % of infertility
• Male factor infertility probably represent the most common cause of infertility.

– Ovulatory disorders (ovulatory factor):

• Prevalence: 30-40 % of female infertility
• Anovulation or oligo-ovulation
• Differential Diagnosis: hypothalamic and pituitary abnormalities, thyroid disease, adrenal disorders, and hyperandrogenic oilgo-ovulation.

– Tubal injury, blockage, paratubal adhesions, or endometriosis (tubal/peritoneal

factor):

• Prevalence: 30-40 % of female infertility
• Damage or obstruction of tubes, usually associated with PID; peritubal and periovarian adhesion, generally resulting from PID, surgery, or endometriosis.

– Abnormalities in cervical mucus-sperm interaction (cervical factor):

• Prevalence: no more than 5 % of cases
• Factors associated with the potential cervical stenosis or poor mucus quality:

? History of exposure to DES

‚ Previous cone biopsy or cauterization of the cervix

ƒ Congenital anomalies

„ Cervicitis

… Anovulation

† Use of Clomiphene citrate for ovulation induction

• Factor associated with poor sperm-cervical interaction: presence of antisperm antibodies

– Rarer conditions, such as uterine abnormalities, immunologic aberrations, and infections:

• Uterine Factors: myoma, congenital uterine malformation, intrauterine adhesion, etc.
• Immunologic Factors: antisperm antibodies, etc.
• Infections: Chlamydial infection, etc.

– Unexplained Infertility

　

1. Work-up for Infertile Couple:

1. History:

­ Medical History: pituitary, adrenal, and thyroid dysfunction？

­ Surgical History: pelvic surgery？

­ OB/GYN History: pelvic inflammatory disease, IUD, coital frequency, dyspareunia, sexual

dysfunction？

2. Physical Examination:

­ Height, weight, body habitus, hair distribution, thyroid gland, status with regard to

galactorrhea, or findings of the pelvic examination, etc.

3. Evaluation of Male Factor:

­ Semen Analysis:

v The basic laboratory study, and should be a part of every infertility workup.

v The basic measurements:

1. Sperm Volume:

- Normal Value: 2-6 ml

2. Sperm Concentration:

- Normal Value: > 20 million/ml

3. Sperm Motility:

- Normal Value: > 50 %

4. Sperm Morphology:

- Normal Value: > 30 % normal forms

v The additional measurements:

1. Numbers of White Cells:

- lymphocytes or immature germ cells

- Normal Value: round cells < 5 million/ml, or leukocytes < 1 million/ml

2. Sperm Penetration Assay (SPA)

3. Human Zona-binding Assay (the Hemizona test)

4. Hypo-osmotic Swelling Test

5. Monoclonal Antibodies: to detect the acrosome reaction

6. ATP Content in the Semen

v If abnormalities in the semen are detected, further evaluation by a urologist is indicated

to diagnose the defect.

4. Evaluation of Ovulatory Factor:

1). Basal Body Temperature:

Ø Biphasic pattern is indicative of ovulation.

2). Midluteal Serum Progesterone:

Ø Timing of measurement: D21-23 of and ideal 28-day cycle

Ø Progesterone level of > 3 ng/ml (10 nmol/l) confirms ovulation.

3). Luteinzing Hormone Monitoring:

Ø A two- to threefold elevation of serum LH levels over vase line is sufficient to

document an LH surge and predict ovulation.

4). Endometrial Biopsy:

Ø Timing of Biopsy: 2-3 days before the expected onset of menses

Ø The finding of secretory endometrium is indicative of ovulation.

5). Ultrasound Monitoring:

Ø Ovulation is characterized by a decreased in follicular size and the appearance of

fluid in the cul-de-sac.

Ø Ovulation occurs when the follicular size between 17-29 mm (mean 21-23 mm).

5. Evaluation of Tubal and Peritoneal Factors:

1). HSG:

Ø Performed between D6-11

Ø for adhesion, sensitivity: 76 %, specificity:83 %.

2). Laparoscopy:

Ø Abnormal finding on HSG should be confirmed by direct visualization with

laparoscopy.

3). Falloposcopy

6. Evaluation of Cervical Factor:

¶ PCT (postcoital test)

7. Evaluation of Other Conditions

　

2. Treatment:

1. Male Factor Infertility:

? Medical Therapy:

Hypothalamic dysfunction ’ GnRH therapy

Retrograde ejaculatory dysfunction ’ α adrenergic agonist

Immunologic dysfunction (antisperm antibodies) ’ condoms and glucocorticoids

Idiopathic infertility ’ Clomiphene citrate

‚ Surgical Therapy: varicocele repair, reversal of vasectomy, etc.

ƒ Artificial Insemination and ART:

² Most common forms of artificial insemination:

processed sperm from the male partner of a donor

² Types of insemination:

• Intrauterine insemination (IUI): most widely practiced
• Intracervical insemination
• Fallopian tube sperm perfusion
• Direct intraperitoneal insemination
• Intrafollicular insemination

² Sperm retain their fertilizing capacity for 24-48 hours after ejaculation if they are

able to escape the intravaginal environment. Oocytes can be fertilized for

approximately 12-24 hours after ovulation

2. Ovulatory Factor Infertility:

{ Patients with ovulatory factor infertility have the greatest success rates with infertility

j Clomiphene Citrate (Clomid, Serophene):

² The first-line regimen for medical induction of ovulation in most patients with

ovulatory infertility

² Mechanism of action: a weak synthetic estrogen, but acting clinically as an

estrogen antagonist for ovulation induction at typical pharmacologic doses

² Ovulation Rate: 80-85 %; Conception Rate: 40 %

² Side effects: infrequent ovarian hyperstimulation syndrome, vasomotor flushes,

nausea, pelvic discomfort, breast pain, and visual abnormalities.

² Clinical Usage:

? Clomiphene (50) 1# qd (D5-D9)

‚ Documentation of ovulation by BBT chart, ultrasound, luteal-phase

progesterone, etc.

ƒ Intercourse qod (D14-D20)

Ovulation is expected to occur 5-10 days after the last day of therapy.

­ If ovulation does not occur at the initial dosage, the dosage in increased in

each subsequent cycle by 50mg/day. (FDA-recommended max. dose

100/day)

k Gonadotropins:

² Indications:

? Women in whom clomiphene citrate has failed

‚ Women with ovulatory dysfunction secondary to hypogonadotropic

hypogonadism.

² Drugs most often used: hMG

- A mixture of FSH and LH purified from the urine of postmenopausal women

- Mechanism of action: stimulating ovarian follicular development

(\ Functional ovarian tissue is necessary for successful therapy.)

- Most important adverse effects: OHSS and multiple gestation

² Typical treatment regimen:

? Patients begin therapy 2, 3, or 4 days after the onset of spontaneous or

induced menses.

‚ Patients with evidence of endogenous estrogenic activity begin therapy by

taking 1 or 2 ampules of hMG (75-150 IU) per day; those with

hypogonadotropic hypogonadism take 1 ampule per day.

ƒ The daily dosage is maintained until cycle day 6 or 7, when the serum

estradiol level is measured to document ovarian response.

„ If no such response has occurred, the hMG dosage is increased by 1 or 2

ampules per day every 3 to 4 days until a response is evidenced by rising

estradiol levels or until a protocol-determined maximal dosage is reached.

… Once an ovarian response is obtained, treatment is typically continued

without a further increase in dose.

† Vaginal ultrasonography and serum estradiol measurements are performed

every 2 or 3 days to evaluate follicular size, number, and quality. Follicular

development is believed to be adequate when maximal follicular diameter

exceeds 16-18 mm, with a corresponding serum estradiol level of 150-250

pg/ml per mature follicle. Serum estradiol levels associated with adequate

folliculogenesis and oocyte maturation vary with follicular number and are

laboratory specific but should be > 600 pg/ml and should not exceed

1500-2000 pg/ml.

‡ When appropriate follicular size and estradiol levels have been attained,

5000-10000 IU of hCG is administered intramuscularly. Ovulation is

expected 36 hours later, so timing of intercourse of insemination may be

planned accordingly. The targeted window for completion of folliculogenesis

is approximately 10-15 days.

² Alternative regimens

l Pulsatile GnRH Therapy:

² Indications:

- Patients with hypothalamic failure and subsequent ovulatory factor infertility

m Bromocriptine and Dexamethasone Supplementation:

n Surgical Treatment:

3. Tubal and Peritoneal Factor Infertility:

 Proximal Tubal Occlusion:

Tubocornual anastomosis (pregnancy rate 44 %)

Transcervical Recanalization (pregnancy rate 31-34 %)

¹ Distal Tubal Occlusiion:

ª Surgical Correction: fimbrioplasty or neosalpingostomy

Patients with both proximal and distal tubal disease represent the poorest

candidates for surgical management of infertility

ª Poor prognostic factors for a successful pregnancy after neosalpingostomy:

? Hydrosalpinx > 30 mm in diameter

‚ Absence of visible fimbriae

ƒ dense pelvic or adnexal adhesions

¼ Peritoneal Factor (Pelvic Adhesion):

If significant peritoneal adhesive disease is believed to be affecting tubal motility or

the access of ova to tubal fibriae, microsurgical adhesiolysis is the treatment of

choice.

¿ Endometriosis-associated Infertility: general recommendations

? Suppression of ovulation with danazol, gestrinone, medroxyprogesterone acetate,

GnRH agonists, and oral contraceptive pills is not effective for this indication;

further trials evaluating their efficacy are unwarranted.

‚ Laparoscopic destruction of endometriotic implants may be effective; larger,

well-designed trials are warranted to determine the effectiveness of this procedure.

ƒ Danazol therapy does not improve upon the results derived from laparoscopy

alone.

„ Conservative surgical therapy via laparotomy may be of benefit, particularly in

cases of severe endometriosis, but further studies are mandatory.

… Danazol therapy offers no advantages over conservative laparotomy alone.

4. Cervical Factor Infertility:

° Surgical Therapy

° IUI: for patients with abnormalities not amenable to surgical therapy

° Ovulation induction combined with IVF, GIFT, or ZIFT: for patients with abnormalities

not amenable to surgical therapy

5. Uterine Factor Infertility: † predominantly surgical therapy

6. Unexplained Infertility:

- Ovulation induction with or without IUI

- IUI

- ART (particularly GIFT)

1. 　
2. Assisted Reproductive Technologies:

1. IVF (In Vitro Fertilization):

¹ Success Rates of Available Techniques: (Table 27.5)

¹ IVF Protocol:

j GnRH agonist downregulation is performed prior to ovulation induction with

gonadotropins.

k Follicular maturation and ovulation are effected with combined hMG/hCG

administration.

l Oocyte retrieval is performed transvaginally, under ultrasonographic quidance.

m Analgesia for oocyte retrieval is provided on an individualized basis but most

commonly involves intravenous sedation or spinal nerve block.

n Embryo transfer is undertaken 48 hours later after oocyte retrieval, when most

embryos have reached the four- to six-cell stage. For standard IVF procedures,

transfer is accomplished via transcervical cannulation and injection of embryos

into the intrauterine cavity.

o Luteal phase support is provided until menses or pregnancy is documented. The

initial evaluation for pregnancy during IVF cycles consists of quantitative β-hCG

measurement 16 days after embryo transfer.

2. GIFT/ZIFT/TET: (Transfer Technique)

¹ Differing from standard IVF transfer regimens: all utilizing the tubal microenvironment

¹ Major difference between these three techniques: time of transfer

± GIFT:

Transfer of recovered oocytes and processed sperm (gametes) immediately

following oocyte retrieval into the fallopian tube, either laparoscopically or

transcervically.

± ZIFT:

Culturing then transfer of fertilized oocytes (zygote-stage embryo) 24 hours

after oocyte retrieval into the fallopian tube laparoscopically.

± TET (Tubal Embryo Transfer):

Transfer of embryos after more than 24-hour culture into the fallopian tube

laparoscopically.

3. Donor Oocytes:

¹ Screening Oocyte Donors

¹ Method of Oocyte Donation: (“mock cycle”, Figure 27.6)

　

Filename: Infertility