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MBBS IV - Junior Clerkship WCS > JC111 (O&G) – Management of Infertility > Flashcards

JC111 (O&G) – Management of Infertility Flashcards

1
Q

Describe the ovarian cycle, follicle development and ovulation

A
  1. 1 follicle develops each month under influence of hypothalamus: GnRH acts on anterior pituitary: LH, FSH
  2. FSH rises in first few days of period (early follicle phase)
  3. Follicle with highest amount of FSH receptor starts to grow gradually&raquo_space; produces estradiol
  4. Estradiol acts on endometrial lining to increase thickness and growth of endometrial glands
  5. When follicle grows to a certain size, estradiol surges rapidly and triggers LH surge&raquo_space; rupture of follicle to release egg
  6. Follicle becomes corpus luteum (luteal phase): produces progesterone which acts on endometrium for it to become secretory to prepare for implant
  7. If woman not pregnant&raquo_space; progesterone level decreases 14 days after release of egg&raquo_space; period
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2
Q

Define the normal monthly and cumulative pregnancy rates

A

Peak monthly pregnancy rate ~30% for women aged 25-30

Cumulative pregnancy rate (measures successfulness of natural conception)
 Cumulative pregnancy rate in 1 year ~ 80%
 Cumulative pregnancy rate in 2 years ~90%

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3
Q

Define infertility

A

failure to establish a clinical pregnancy
 After 12 months of regular unprotected sexual intercourse; or
 Within 6 months in >35 years

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4
Q

Causes of infertility in female

think causes of HPO axis dysfunction

A

Ovulatory dysfunction/ anovulation

  1. Hypothalamic:
    - Weight change, obesity, anorexia
    - Tranquilizers, psychiatric drugs
    - Psychological disturbance
  2. Pituitary
    - Tumor
    - Sheehan syndrome (anterior pituitary infarct)
    - Hyperprolactinaemia/ Prolactinoma
  3. Ovary
    - Ovarian insufficiency/ failure
    - Chromosomal disorders (Turner’s)
    - Iatrogenic damage
    - PCOS
  4. Endocrine
    - Thyroid and adrenal diseases
  5. Corpus:
    - Tubal lesions
    - Endometriosis
  6. Others:
    Cervical, immunological, coital dysfunction
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5
Q

Causes of infertility in male

A

Sperm production defects:

  1. Testicle/ endocrine disorders:
    - Hypothalamic-pituitary disorders
    - Hypogonadotrophic hypogonadism
    - Hyperprolactinaemia
2. Primary testicular disease
 Chromosomal: Klinefelter’s Syndrome (47XXY)
 Varicocoele, testicular hyperthermia
 Infections: mumps
 Trauma (torsion of testes)
 Cryptorchidism
 Previous radiotherapy/chemotherapy
  1. Genetic – Y chromosome microdeletions: 3 deletion regions (AZFa-c) of Yq11

Sperm obstructive defects:
 Infection
 Congenital absence of vas
 Surgery – vasectomy

Coital dysfunction

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6
Q

Top 5 most common causes of infertility

A

Female:

  • Ovulatory dysfunction/ anovulation
  • Tubal problems
  • Endometriosis

Male factors: subnormal sperm

Unexplained after exclusion

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7
Q

Endometriosis

  • Cause
  • Investigation and typical findings
  • Complications
A

Cause:

  • retrograde of menstrual blood from cervix and vagina into uterus
  • Some blood retrograde flows through Fallopian tubes to peritoneum or surface of ovary
  • Formation of cysts in the pelvis

Investigation:
 Ultrasound reveals chocolate cyst (old blood), homogeneous low echogenicity
 Laparoscopy reveals small dark/ bluish round deposits on peritoneal cavity

Complications: cause adhesions behind uterus/ between peritoneal surface and ovary
 Tubal blockage, dysmenorrhea, dyspareunia

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8
Q

Outline history taking questions for a couple with suspected infertility

A 
Female: 
 Age
 Menstrual cycle (regularity)
 History of pelvic infection
 Surgical history (pelvic adhesions)
 Previous investigations, treatment

Male:
 Age
 Occupation (exposure to high temperature/ chemicals
 Past health
 Coital history (problem in erection/ ejaculation; no. of intercourse per week)
 Smoking, alcohol (affect sperm production)

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9
Q

Outline P/E for female and male with infertility

A

Female:
Body weight (PCOS risk)
Vaginal examination:
 Uterine size (increase in endometriosis, uterine fibroid)
 Mobility (less mobile in pelvic adhesions, endometriosis)
 Adnexal mass (chocolate cyst)

Male: 
 Testicular size
 Vas (present?)
 Epididymis (engorged in obstructive azoospermia)
 Varicocele (impaired semen parameters)
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10
Q

Indications for referring an infertile female to reproductive centers

A 
 >35 years old
 Irregular cycles
 Previous sexually transmitted disease (STD) (affects tubes)
 Previous pelvic surgery (adhesions)
 Abnormal pelvic examination
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11
Q

Indications for referring an infertile male to reproductive centers

A 
 Systemic illness
 Previous genital pathology
 Previous STD
 Varicocele
 Abnormal genital examination
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12
Q

Investigations for male infertility

A
  1. semen analysis (SA) ***
  2. Hormonal assays: FSH, prolactin, testosterone
  3. Karyotype and Y microdeletion for testicular failure (for very low sperm count <2million/mL)
  4. Vasogram (obstructive azoospermia)
  5. Testicular biopsy (differentiate obstructive or non-obstructive)
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13
Q

Semen analysis

  • Collection method
  • Benefits
  • Drawbacks
  • Criteria for fertility
A

Collection:

  • masturbate and collect into sterile bottle at home or hospital
  • Store at body temperature before submission

Benefits:

  • Simple, non-invasive
  • Low count can indicate assisted reproduction

Drawbacks:

  • Requires trained technician
  • Low predictive value: Extensive overlap between fertile vs. infertile

Criteria:
 Volume >1.5 ml
 Concentration >15 million/ml
 Motility: >=32% forward motility

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14
Q

Investigations for female infertility

A
  1. Test of ovulation by pregnancy or inferential tests:
    - Serum progesterone level at mid-luteal phase
    - Basal body temperature
    - Urine LH kits
    - Pelvic ultrasound
  2. Test for cause of anovulation (HPO axis, thyroid and adrenal tests)
  3. Tubal patency test
    - Hysterosalpingogram (HSG)
    - Laparoscopy
  4. Endometrial biopsy
  5. Thrombophilia and immunologic testing (recurrent miscarriage)
  6. Karyotype (premature ovarian insufficiency)
  7. Postcoital testing (check cervical mucus for presence of sperm after intercourse):
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15
Q

List 4 tests for female ovulation
Rationale of each test
Drawbacks to each test

A
  1. Serum progesterone levels:
    - Taken in the mid-luteal phase
    - >3 ng/mL = presumptive recent ovulation
    - Drawback: Progesterone released in pulsatile manner, large fluctuations over hours
  2. Basal body temperature (BBT)
    - Corpus luteum release progesterone to increase BBT. Measure temp for 3-4 months
    - BBT nadir (lowest point) = ovulation
    - Drawback: not accurate to time intercourse, difficult to interpret
  3. Urine LH kits:
    - Positive LH = indication for sex
    - Drawback: psychological stress
  4. Pelvic ultrasound:
    - observe signs of ovulation
    - Drawback: repeated scans are labor intensive and expensive
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16
Q

Signs of ovulation on pelvic ultrasound

A

 Progressive follicular growth (follicle appears as dark shadow)
 Sudden collapse of the pre-ovulatory follicle
 Loss of clearly defined follicular margins
 Appearance of internal echoes within the corpus luteum (bleeding)
  cul-de-sac fluid volume (fluid in pouch of Douglas)

17
Q

Investigations for anovulation

18
Q

Hysterosalpingogram (HSG) for infertility Ix

  • benefits, drawback, indication
A

Hysterosalpingogram (HSG): saline insufflation with radio-opaque dye
- Benefit: Less invasive, Allows assessment of uterine cavity

  • Drawbacks:
    Pain and spasm in proximal end leads to false positive
    Cannot detect peritubal adhesions
    Pelvic inflammatory disease (4-5%), must check chlamydia infection before instrumentation

Indication:
 No comorbidities such as previous PID/ ectopic pregnancy
 No clinical s/s of endometriosis

19
Q

Laparoscopy for infertility investigation

  • Benefits
  • Drawbacks
  • Indications
A

Laparoscopy: inflate peritoneal cavity with CO2 and directly observe pelvic structures

Benefits:

  • Higher accuracy than hysterosalpingogram
  • Diagnostic/ therapeutic for endometriosis and pelvic adhesions (diathermy, biopsy, ligation…)
  • Can observe peri-tubal obstructions

Drawback:

  • GA risk
  • Invasive

Indication:
- Infertile women with comorbidities

20
Q

Pre-pregnancy advice for infertile male and female

A

Female:

  • Folic acid supplement (0.4mg) around conceiving and first 12 weeks of pregnancy
  • Control body weight
  • Stop smoking and alcohol (miscarriage, congenital abnormalities, fetal alcohol syndrome)

Male:
 Stop smoking
 Avoid excessive alcohol
 Men with poor quality sperm advised to:
Wear loose fitting underwear and trousers
Avoid occupational or social situations that might cause testicular hyperthermia (e.g. spas)

21
Q

Ovulation induction therapy options

  • For hyperprolactinemia, ovarian insufficiency, PCOS and hypothalamic anovulation
A

For hyperprolactinaemia

  • Exclude pituitary tumor
  • Suppress prolactin with Bromocriptine, Cabergoline

For Ovarian insufficiency (High FSH)
- Donor eggs, IVF

For PCOS, hypothalamic cause

  • Optimize weight
  • Surgical ovarian drilling (reduce intra-ovarian testosterone)
  • Medical induction:
    i) Clomiphene citrate
    ii) Letrozole
    iii) Recombinant Gonadotrophin injection
22
Q

Clomiphene citrate

MoA

S/E

Effectiveness

A

Anti-oestrogen acting at hypothalamus, remove negative feedback of estrogen on HP axis

S/E: 
 Hot flushes
 Multiple pregnancy
 Ovarian cysts
 Abdominal distension/ pain
 Blurring of vision

Effectiveness:
Ovulation rate 50-80% in 6 cycles
Pregnancy rate 30-50% in 6 cycles

23
Q

Letrozole

  • Indication
  • MoA
  • Side effects
A

Indication: First line for infertility due to PCOS

MoA: Aromatase inhibitor

S/E: Nausea, SoB due to pleural edema, ascites, reduce urine output

24
Q

Recombinant gonadotropin

  • MoA
  • S/E
A

MoA: Acts directly on ovaries (very effective)

S/E:

  1. OHSS (ovarian hyperstimulation syndrome)
    - Abdominal distension (fluid accumulation)
    - pleural edema/ pericardial cavities causing SOB, palpitations
    - Nausea (high estrogen)
    - Collection of fluid in third space
  2. Multiple pregnancy
25
Q

Treatment options for infertility caused by endometriosis (mild/ moderate)

A
  1. Surgical ablation (diathermy or laser)
  2. Ovarian stimulation and intrauterine insemination
    - Give hCG to stimulate ovulation, timely insemination when LH surge
  3. In vitro fertilization and embryo transfer (IVF-ET)
26
Q

Key steps in IVF treatment

A
  1. Ovarian stimulation: by GnRH agonist
  2. Oocyte pickup: Give hCG to separate egg from granulosa cells, arrange egg retrieval 36 hr after hCG
  3. Fertilization:
    - conventional insemination: mix sperm with egg in culture medium (for normal sperm)
    - Intracytoplasmic sperm injection (ICSI): inject single sperm into an egg (for poor sperm)
  4. Examine zygote division and choose embryos developing into blastocysts (High grade = regular blastomeres)
  5. Embryo transfer with fine catheter and USG (through vagina into uterine cavity)
    - Replace 1 embryo to reduce risk of multiple pregnancies
    - Place 2 embryos if >38 years old and 2 failed IVF
27
Q

Treatment options for infertility caused by tubal obstruction

A
  • Tubal surgery:
    1. Adhesiolysis (separate adhesions)
    2. Re-anastomosis (proximal blockage: remove blocked area and do anastomosis)
    3. Salpingostomy
    Approaches:
     Laparotomy vs. laparoscopy
     Microsurgical technique
  • In-vitro Fertilization and Embryo Transfer (IVF + ET)
28
Q

Treatment options for male infertility (Effective options only)

  • Obstructive causes, endocrine tx, artificial methods
A

Obstructive azoospermia:
 Varicocele treatment (ligate varicocele/ block vessels)
 Vasectomy reversal/ overcome correctable obstruction (restore patency)
 Microsurgical epididymal sperm aspiration (MESA)

Endocrine:
 Gonadotrophins/ GnRH for hypogonadotrophic hypogonadism
 Bromocriptine for sexual dysfunction associated with hyperprolactinaemia

Testicular failure/ Non-obstructive azoospermia
Testicular sperm extraction (TESE)

Artificial inseminations:
 Ovarian stimulation and intrauterine insemination
 IVF/ET - In-vitro Fertilization and Embryo Transfer (IVF + ET)

29
Q

Treatment options for unexplained infertility and coital problems

A

Unexplained infertility:

  1. Expectant treatment (e.g. young woman tried for 1 year&raquo_space; ask to try for another year)
  2. IVF treatment

Coital problems:

  1. Psychotherapy
  2. Drugs for erectile dysfunction e.g. viagra
  3. Artificial insemination

Not recommended:

  • Clomid/ (clomiphene citrate (risk of multiple pregnancies)
  • unstimulated intrauterine insemination (unstimulated IUI)

MBBS IV - Junior Clerkship WCS (131 decks)

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