Infertility – SOGC 2011

Infertility

  • No conception after 12 months of unprotected and frequent intercourse
  • Primary – no previous pregnancy
  • Secondary – after previous pregnancy

1 When a patient consults you with concerns about difficulties becoming pregnant:
a) Take an appropriate history (e.g., ask how long they have been trying, assess menstrual history, determine coital frequency and timing) before providing reassurance or investigating further.
b) Ensure follow-up at an appropriate time (e.g., after one to two years of trying; in general, do not investigate infertility too early).

Etiology:
  1. Female:
    • ovulatory dysfunction 15-20%: PCOS, POF, prolactinoma, thyroid dz, cushing’s syndrome
    • Uterine / tubal factors: PID, adhesions, asherman syndrome, previous ectopic, uterine anomaly, IUD, fibroids
    • Cervical factors: structural imperfections, hostile mucous, cervical stenosis
    • Peritoneal factors: endometriosis
  2. Male
    • idiopathic
    • 1o hypogonadism / 2o hypogonadism
      • Testicular: vericocele, post-infectious / cryptorchidism (STI, mumps, TB), torsion
      • Androgen insensitivity, klinefelters
      • Iatrogenic: radiation, drugs (marijuana)
      • Structural: vasectomy, hernia repair
    • Altered sperm transport
      • obstructed / absent vas deferens
      • Retrograde ejaculation
Hx:
1) ovulatory dysfunction, 2) risk factors for tubal infertility, 3) sexual factors, and 4) male or sperm factors
  1. Female:
    • LMP, cycle, regularity, intermenstrual bleeding, changing – regular menses q 24 to 35 days associated with premenstrual molimina (breast tenderness, bloating, cramping, mood changes) is compatible with ovulation in at least 95% of women
    • A history of very irregular cycles suggests anovulation

      further evaluation for its various causes, including PCOS, hyperprolactinemia, thyroid dysfunction, premature ovarian failure, and hypothalamic dysfunction (eg, eating disorder, excessive exercise)

    • GTAPL, SA?,
    • Coitus: coital frequency, lubricants, Prev Paps
    • PMH: PID, Sx
    • ROS / systemic symptoms
      1. POF: hot flashes, vaginal dryness
      2. PCOS: hirsutism, acne, alopecia, increased wt
      3. Prolactinoma: h/a, vision change, galactorrhea / lactation
      4. Endometriosis: dysmenorrhea, dyspareunia, dyschezia
      5. Endocrine: thyroid, cushing’s turner’s
  1. Male:
    • Erections, ejaculation, libido, coital frequency, lubricants,
      • DM (erectile dysfunction)
    • Sperm
      • Underwear – boxers / briefs better (lower temp)
      • Trauma / fevers / infections (TB, mumps, STI)
    • Previous successful pregnancies
    •  ROS / systemic symptoms
      • Gynecomastia, lack of body hair, hypospadias
      • Klinefelter’s: tall, thin, gynecoid appearance
  2. Past Sx: damage, adhesions
  3. PMH: STI, PID, chemo
  4. Family Hx: congenital / chromosomal abnormalities
  5. Medications: OCP, advice daily folic acid
PEx

Women

  • BMI, thyroid, breasts
  • signs of hyperandrogenism: hirsutism, acne, acanthosis nigricans
  • Bimanual: search for signs of endometriosis or pelvic adhesions, such as a fixed retroverted uterus, adnexal masses or tenderness, and uterosacral ligament thickening, nodules, or tenderness
  • Pap + swabs

Male: Testicles: vericocele, testicular size, hernias, masses

Ix / referral timing:
  1. 35-40: after 6mo
  2. >40: immediately
  3. Sooner if
    • Female with hx of moderate-severe endometriosis
      • PID / STI, amenorrhea, pelvic pain
      • pref pelvic Sx, chemo / XRT
      • recurrent pregnancy loss
    • Male with abnormal semen analysis, STI, urogenital sx, varicocele

2 In patients with fertility concerns, provide advice that accurately describes the likelihood of fertility.

Likelihood of fertility
  1. 75% couples achieve pregnancy in 6mo, 85% in 1yr, 90% in 2 yr
  2. The monthly conception rate of couples at peak fer- tility is 20% to 25%.
  3. Mean time to conception (ie, the time at which 50% of women have conceived) increases with age from 4 months in women younger than 30 to 9 months in women older than 35.
  4. 10-15% dx with infertility – 10-15% idiopathic, 1/3 female factor, 1/3 male, 1/3 combined
  5. Women in their 20s and 30s should be counselled about the age- related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care .
  6. Incidence of spontaneous abortion almost doubles among women in their late 30s, compared with women < 30.
  7. Natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s .
  8. The risk of SA and chromosomal abnormalities increases with age . Women should be counselled about and offered appropriate prenatal screening once pregnancy is established .
Pre-conception counselling
  1. regarding the risks of pregnancy with advanced maternal age,
  2. promotion of optimal health
    • Smoking cessation (risk of ectopic, SA, infertility, adverse pregnancy outcome)
      • Second hand smoke is also a concern
    • Wt control
    • Avoid EtOH / drug – Marijiuna inhibit GnRh in both male and female
    • NSAIDs could block oocyte release (interfere ovulation)
  3. if >40yo – screening for concurrent medical conditions, eg. HTN, DM etc
  4. Ovulation tracking, optimal intercourse timing
    • Optimal timing for intercourse is 5 days before until 2 days after the predicted day of ovulation.
    • Best chance: 48 hours before until 24 hours after ovulation
    • If couples are not making any particular effort to time intercourse around ovulation, then regular frequency of intercourse every 2 or 3 days (ie, two or three times weekly) should be encouraged.
  5. Ensure Immunization UTD
    1. A serum rubella titre should be measured to confirm immunity (>10) and booster vaccination given if necessary 1 month before attempted pregnancy.3
  6. All women considering pregnancy should take folic acid (0.4 mg/d minimum) to reduce the chances of having babies with neural tube defects

3 With older couples who have fertility concerns, refer earlier for investigation and treatment, as their likelihood of infertility is higher.

  1. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive .
  2. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age .
    • Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation .
  3. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia . Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small .

4 When choosing to investigate primary or secondary infertility, ensure that both partners are assessed.

Ix: 3 main area – 1) ovulation, 2) Tubal function, 3) male factors
1st line:
  1. Ovulation testing – b/w only if abnormal
    • B/W: Day 3 LH/ FSH (POF) /Prolactin/ TSH/estradiol/DHE
  2. a semen analysis
  3. assessment of tubal patency, usually by hysterosalpingogram (HSG).

1) Swabs r/o STI – both partners

2) Female:

  • If ovulation is in doubt (regular cycles), it can be confirmed using basal body temperature (BBT) charting (up to 3mo of charting) -A rise in BBT occurs 2 or 3 days after ovulation and is an indirect assessment of ovulation or using urinary ovulation detection kits

    or by measuring the serum progesterone level in the midluteal phase: Day 21 progesterone (7d before before expected period or after ovulation)

  • Day 3 LH/FSH/Prolactin/TSH/estradiol/DHE
  • Karyotype
  • Rubella, varicella serology – vaccination if not immune
  • Pelvic u/s r/o myomas, ovarian cysts
  • HSG – ensure tubal patency – can be therapeutic
  • Hysteroscopy: visualize the uterine cavity

3) Male:

  • Semen analysis: count >20million, motility >50%, vol 2-5ml, morphology >30%, pH, WBC <1mil/ml
    • req 3-6 days abstinence
  • Free Testosterone
  • karyotyping

4) Ovarian reserve testing (Day 3 FSH > 15 = decreased reserve) may be considered for women ≥ 35 years of age

  • or for women < 35 years of age with risk factors for decreased ovarian reserve such as,
    • a single ovary, previous ovarian surgery,
    • poor response to follicle-stimulating hormone,
    • previous exposure to chemotherapy or radiation,
    • or unexplained infertility .

5 In couples who are likely infertile, discuss adoption when the time is right. (Remember that adoption often takes a long time.)


Tx:

  • Lifestyle: Wt control, smoking cessation, NO EtOH & caffeine, increase frequency of coitus
  • Azoospermia / oligospermia – Donor sperm
  • Uterus: Surgery for leiomyomas, synechia/septa or congenital anomalies; laparoscopic sx for endometriosis
  • Cervix: Consider intrauterine implantation of sperm (IUI),  ICSI – intraCytoplasmic Sperm Injection, or IVF to bypass cervix
  • Tubes: HSG (hysterosalpingography) to ensure and tx patency of tubes. Sx Tuboplasty – tubal reconstruction, adhesionlysis, salpingectomy & consider IVF
  • Anovulation
    • Med: Clomiphene / SERMs to stimulate ovulation, ± metformin (PCOS); dopamine (hyperprolactinoma)
    • surgery: pituitary tumor ; wedge resection / drilling of ovary (PCOX)

Consider discussing adoption if Tx failed


6 In evaluating female patients with fertility concerns and menstrual abnormalities, look for specific signs and symptoms of certain conditions (e.g., polycystic ovarian syndromehyperprolactinemia, thyroid disease) to direct further investigations (e.g., prolactin, thyroidstimulating hormone, and luteal phase progesterone testing).

PCOS:
  • Etiology: Steady GnRH production → no LH surge to induce ovulation
  • common in 15-35yo
  • Symptoms:
    • Anovulation – Amenorrhea / oligomenorrhea / infertility / menorrhagia
    • obesity (not always), insulin resistance, acanthuses nigricans
    • hyperandrogenism: hirsutism, acne
    • bilaterally enlarged polycystic ovaries
  • Fam Hx: 40% sister, 20% mother with PCOS
  • Ix:
    • Transvaginal U/S – polycystic ovaries
    • LH:FSH >2:1, increased DHEAS, increased free Testosterone
    • Fasting glucose
  • Tx
    • Cycle control with wt loss, increased exercise, OCP, Metformin
      • Tranexamic acid for menorrhagia
    • Infertility Tx with wt loss
      • Clomifene ± metformin to induce ovulation
    • Hirsuitism
      • OCP ± spironolactone for antiandrogen effect
Hyperprolactinemia:
  • Galactorrhea, amenorrhea
  • H/A, visual disturbances if pituitary tumour
  • Tx: Bromocriptine
Hyperthyroidism:
  • Anxiety, tremor, palpitation, wt loss, heat intolerance, increased appetite, oliogomenorrhea / amenorrhea

References:


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Posted in 52 Infertility, 99 Priority Topics, FM 99 priority topics, Gyne

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