Stat Consult: Infertility in Women

Background

• Infertility is the inability to conceive after 1 year of regular unprotected sexual intercourse
• It occurs in about 15% of reproductive elderly couples worldwide and is more common in developing countries.
• Causes of infertility can be multifactorial and include:
  • Combined male and female factors in about 40%
  • Male factor infertility in about 26% -30%
  • Ovulation disorders at about 21% -25%
  • Tubal factors in about 14% -20%
  • Cervical / uterine / peritoneal disorders in approximately 10% -13%
  • Idiopathic in about 25% -28%
• Diagnosis usually based on history and physical; both partners are evaluated simultaneously

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Pathogenesis in women

• Ovulation Disorder Infertility
  • Occurs when ovaries do not produce mature oocyte on a regular basis due to hypothalamic dysfunction, polycystic ovary syndrome (PCOS), ovarian failure and / or hyperprolactinemia
• Tubal factor infertility occurs when fallopian tubes fail to capture ovulated ovaries and / or transport sperm and embryos due to:
• Uterine factor infertility occurs when the uterus does not allow embryos to be implanted and / or does not support normal embryonic growth and development due to:
  • Congenital uterine disorders
  • Endometrial polyps
  • Intrauterine synechiae with adhesion of myometrium to opposing uterine wall
  • Uterine leiomyoma
• Cervical factor infertility occurs when cervix fails to trap or transport sperm in the uterus and fallopian tubes due to reduced cervical mucus quality / quantity or cervical conization

History and Physical Examination

• Infertility history
  • Duration of infertility
  • Menstrual history
  • Sexual activity, including frequency and timing (relative to cycle) of coitus
  • Previous method of contraception (especially intrauterine device)
• Previous medical history
  • Previously abnormal pap smears

• Physically
  • Measure height / weight
  • Evaluate skin – hirsutism (acne on the face and / or breast may indicate hyperandrogenism); vitiligo can indicate autoimmune systemic disease
  • Evaluate for thyroid disorders
  • Evaluate for breast changes
  • Examining stomach for organomegaly, ascites, surgical scars
• Do pelvic exam, assess for:
  • Vaginal, cervical or adnexal abnormality
  • Size, shape, mobility and position of uterus
  • Nodules or tenderness in posterior dead end (may indicate endometriosis / tuberculosis)

Diagnosis

• Infertility evaluation is indicated
  • After 1 year of regular unprotected sexual intercourse for women <35 years old without known risk factors for infertility
  • After 6 months of regular unprotected intercourse in couples with woman> 35 years and / or in couples with known clinical causes or predisposing factors for infertility
  • Immediately in women> 40 years of age, or if there is a clear cause for infertility / subfertility

• Initial evaluation to assess ovulatory function
• Assessment of tubal transparency

• Test ovarian reserve
• Test for suspected uterine abnormalities
  • Hysteroscopy considered as definitive method for diagnosis and treatment
• Test for suspected pelvic disorders
  • Laparoscopy may be indicated to confirm diagnosis in women with unconvincing results on less invasive tests
• Other tests include
  • Serum Thyroid Stimulating Hormone (TSH)
• Endometrial biopsy not indicated for detection of luteal phase deficiency

Management

• Treatment of infertility is based on the underlying cause
  • For anovulation (WHO classified anovulation in groups)
    • WHO Group I: hypogonadotropic hypogonadism (hypothalamic pituitary failure):
      • If BMI is <19, recommend weight gain and / or exercise moderation
      • First-line treatment includes ovulation induction with gonadotropins with luteinizing hormone activity or pulsed administration of gonadotropin-releasing hormone
      • Second-line treatment is IVF
    • WHO Group II: Normogonadotropic Normostrogenic Anovulation (PCOS):
      • Weight loss can improve pregnancy outcomes if BMI is ≥ 30.
      • First-line treatment includes ovulation induction with clomiphene, metformin or both
      • Second-line treatment may include laparoscopic ovarian augmentation or ovulation induction with gonadotropins
      • Third-line treatment is IVF
    • WHO Group III: hypergonadotropic hypoestrogenic anovulation (primary ovarian insufficiency), first-line therapy is IVF with donated oocytes
  • For hyperprolactinemic amenorrhea, treatment includes therapy with dopamine agonists (such as bromocriptine or cabergoline)
  • For fallopian tube disorders:
    • Tubal microsurgery or laparoscopic tuba surgery can restore tubal transparency in patients with mild tubal disease
      • For patients with hydrosalpinx, consider laparoscopic salpingectomy before IVF
  • For amenorrhea and intrauterine adhesions, hysteroscopic adhesiolysis offers to restore normal menstruation and increase the likelihood of conception
  • For endometriosis-associated infertility, options include surgery or assisted reproductive technology (ART).
  • For idiopathic infertility:
    • Advise patients to try to conceive naturally for 2 years; to increase the chance of conception:
      • Frequent unprotected intercourse (2-3 times / week) near the time of ovulation
    • Community on several days during the fertile window (5 days before and the day of ovulation)
  • Consider IVF after 2 years of failed expectant management
  • Intrauterine insemination (IUI) should not be offered regularly to patients with idiopathic infertility
• Ovarian hyperstimulation syndrome (OHSS)
  • Reported in approximately 1.4% of all IVF cycles
  • Considered the most serious complication due to controlled ovarian hyperstimulation in ART
  • Symptoms range from mild abdominal distension to organ failure or death

Prognosis

• Probability of conception in fertile women <40 years old and with regular, unprotected sexual intercourse:
  • 20% -25% per propagation cycle
  • 60% within the first 6 months
  • 84% within 1 year
  • 92% within 2 years
• Factors related to increased chance of conception in women with infertility
  • Short duration of infertility
  • Previous fertility
  • Age <40 years
  • Ideal body mass index (> 19 and <30)
• Approximately 50% overall pregnancy rate after infertility treatment
  • 5% after timely handling
  • 10% after superovulation with IUI
  • 15% -25% on ART

Fertility conservation

• In patients being treated for cancer
  • Consider oocyte / embryo cryopreservation in adolescents / patients of reproductive age who are at risk of infertility due to planned cancer treatments in cases where patients are good enough to undergo ovarian stimulation / oocyte collection
  • Consider ovarian tissue cryopreservation for patients requiring emerging chemotherapy or radiotherapy (which allows no time for oocyte stimulation and recovery)

Kendra Kerk, MS, PA-Cis a physician assistant at Dana-Faber Cancer Institute / Brigham & Women’s Hospital and is also an associate deputy editor for DynaMed, an evidence-based point-of-care database.

Sources

1. National Institute of Excellence in Healthcare. Fertility problems: assessment and treatment. Updated September 2017. Accessed 29 June 2022. https://www.nice.org.uk/guidance/cg156
2. O’Flynn Norma. Assessment and treatment for people with fertility problems: Good guideline. Br J Gen Practice. 2014; 64 (618): 50-51. doi: 10.3399 / bjgp14X676609
3. Kamel RM. Managing the Infertile Couple: An Evidence-Based Protocol. Reprod Biol Endocrinol. 2010; 8:21. doi: 10.1186 / 1477-7827-8-21
4. Lindsay TJ, Vitrikas KR. Evaluation and treatment of infertility. Is Fam Doctor. 2015; 91 (5): 308-314; Correction. Is Fam Doctor. 2015; 92 (6): 437.
5. Danis P. Natural reproductive technology for the treatment of infertility. Is Fam Doctor. 2015; 92 (8): 668.
6. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile woman: a committee opinion. Fertile Sterile. 2015; 103 (6): e44-e50. doi: 10.1016 / j.fertnstert.2015.03.019