Infertility: A Comprehensive Guide for MCCQE1 Preparation

Introduction

Infertility is a common clinical presentation in Canadian family practice and gynecology. For MCCQE1 preparation, it is crucial to understand the definitions, the systematic approach to investigation, and the Canadian-specific management guidelines (SOGC).

According to Canadian epidemiological data, approximately 1 in 6 couples in Canada experience infertility. The prevalence has effectively doubled since the 1980s, largely due to delayed childbearing.

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Clinical Definition: Infertility is defined as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.

Exception: Evaluation should begin after 6 months if the female partner is ≥ 35 years old or immediately if there is a known cause (e.g., history of oligomenorrhea, pelvic inflammatory disease, or undescended testes).

Etiology and Classification

Infertility can be classified as Primary (no prior pregnancy) or Secondary (at least one prior pregnancy). The causes are generally distributed as follows:

Male Factor: ~30%
Female Factor: ~40% (Ovulatory dysfunction, Tubal/Pelvic pathology)
Combined Factors: ~20%
Unexplained: ~10%

CanMEDS Health Advocate

Infertility carries a significant psychological burden. Canadian physicians must recognize the emotional toll and advocate for access to resources, including psychological support and fertility treatments, which have varying funding coverage across Canadian provinces (e.g., Ontario’s funded IVF program vs. other provinces).

Differential Diagnosis

Female Factors

1. Ovulatory Dysfunction (WHO Classes):

Class 1 (Hypogonadotropic Hypogonadal): Functional hypothalamic amenorrhea (low BMI, stress, exercise).
Class 2 (Normogonadotropic Normogonadal): PCOS (Most common cause), hyperprolactinemia, thyroid disease.
Class 3 (Hypergonadotropic Hypogonadal): Premature Ovarian Insufficiency (POI), Turner syndrome.

2. Tubal and Pelvic Pathology:

Pelvic Inflammatory Disease (PID) → Tubal occlusion.
Endometriosis.
Previous tubal surgery.

3. Uterine Factors:

Submucosal fibroids.
Polyps.
Congenital anomalies (e.g., septate uterus).
Asherman’s syndrome.

Initial Evaluation (The Work-up)

For MCCQE1, remember that infertility is a couple’s diagnosis. Both partners should be evaluated simultaneously.

1. History Taking Checklist

Use this task list to ensure a comprehensive history:

Frequency & Timing of Intercourse: Are they timing it with the fertile window?
Menstrual History: Cycle length, regularity, molimina (suggests ovulation).
Obstetric History: Gravidity, parity, complications.
Medical/Surgical History: PID, STIs, pelvic surgeries, chemotherapy/radiation.
Medications: NSAIDs (may affect ovulation), spironolactone, testosterone.
Social History: Smoking, alcohol, recreational drugs, occupation (environmental toxins).
Male Specific: History of mumps, testicular trauma, erectile dysfunction.

2. Physical Examination

Female: BMI, signs of androgen excess (hirsutism, acne), thyroid exam, galactorrhea, pelvic exam (tenderness, masses, fixed uterus suggestive of endometriosis).
Male: BMI, urethral meatus placement (hypospadias), testicular volume/consistency, presence of varicocele (palpable “bag of worms”), presence of vasa deferentia.

3. Diagnostic Investigations

Follow this stepwise approach for the initial work-up:

Step 1: Semen Analysis

This is the most non-invasive and cost-effective initial test. If abnormal, repeat in 4-6 weeks (spermatogenesis cycle is ~72 days).

Key Parameters (WHO 2010/2021): Volume, Concentration, Motility, Morphology.

Step 2: Confirm Ovulation

Mid-luteal Progesterone: Measured on Day 21 of a 28-day cycle (or 7 days before expected menses). Level >10 nmol/L confirms ovulation; >30 nmol/L is robust.
TSH & Prolactin: Rule out thyroid disease and hyperprolactinemia.
FSH & Estradiol (Day 3): To assess ovarian reserve (especially if age >35).

Step 3: Assess Anatomy (Tubal Patency & Uterus)

Hysterosalpingogram (HSG): Gold standard for tubal patency. Also evaluates uterine cavity.
Sonohysterogram (SHG): Superior for uterine cavity (polyps, fibroids) but does not assess tubes as well as HSG unless HyCoSy (contrast) is used.

Ovarian Reserve Testing

This is crucial for counseling regarding the urgency of treatment and likelihood of success with IVF.

Test	Timing	Interpretation
FSH	Day 3 of cycle	>10-15 IU/L suggests diminished reserve.
Estradiol	Day 3 of cycle	High levels (>200-250 pmol/L) can falsely suppress FSH, masking diminished reserve.
AMH	Any time	Anti-Müllerian Hormone. Low levels suggest low follicle number. Not cycle-dependent.
AFC	Early follicular	Antral Follicle Count via transvaginal ultrasound.

Management Strategies

Management is directed by the underlying etiology.

1. Lifestyle Modification

Smoking cessation (Both partners).
Weight optimization (BMI 18.5–24.9). Even a 5-10% weight loss in PCOS can restore ovulation.
Folic acid supplementation (0.4 mg - 1.0 mg daily; 5.0 mg for high-risk groups including obesity and diabetes).

2. Ovulation Induction (OI)

Used primarily for WHO Class 2 (PCOS).

Letrozole: Aromatase inhibitor. First-line agent for PCOS in Canada (higher live birth rates than clomiphene).
Clomiphene Citrate: SERM. Second-line. Risk of thin endometrium and multiple gestation (~8%).
Gonadotropins (FSH/LH): Injectables. Higher risk of multiples and OHSS.

3. Assisted Reproductive Technologies (ART)

Intrauterine Insemination (IUI): Used for mild male factor, cervical factor, or unexplained infertility. Requires patent tubes.
In Vitro Fertilization (IVF): Used for tubal blockage, severe male factor, endometriosis, or failed IUI.
ICSI (Intracytoplasmic Sperm Injection): A single sperm is injected into an egg. Standard for severe male factor or surgical sperm retrieval.

4. Surgery

Laparoscopy: For endometriosis ablation or lysis of adhesions.
Hysteroscopy: For resection of septums, polyps, or submucosal fibroids.
Varicocelectomy: Considered if palpable varicocele, abnormal semen, and female partner has normal fertility.

Key Points to Remember for MCCQE1

High-Yield Facts

Age is the single most important prognostic factor for female fertility.
Semen Analysis is the first investigation to order (non-invasive).
Letrozole is the preferred first-line ovulation induction agent for PCOS in Canada (SOGC Guidelines).
HSG is contraindicated if there is an active pelvic infection.
Rubella Immunity should be checked in all women attempting pregnancy (live vaccine, cannot be given during pregnancy).
Unexplained Infertility is a diagnosis of exclusion; management usually progresses from expectant → IUI + OI → IVF.

Mnemonics

Causes of Male Infertility: “VARICO”

Varicocele
Autoimmune (Antisperm antibodies)
Replacement (Hormones/Steroids)
Infection (Mumps)
Congenital (CF, Klinefelter)
Obstruction

Sample Question

Question

A 29-year-old female presents to your office with her 31-year-old husband for infertility evaluation. They have been trying to conceive for 18 months without success. The patient has a history of irregular menstrual cycles occurring every 35 to 45 days and has noted increased hair growth on her chin. Her BMI is 32 kg/m². Her husband’s semen analysis is normal. An HSG confirms patent fallopian tubes. Which one of the following is the most appropriate initial pharmacologic management for this patient?

Explanation

The correct answer is:

C. Letrozole

Explanation: This patient presents with classic signs of Polycystic Ovary Syndrome (PCOS): oligomenorrhea (irregular cycles), clinical hyperandrogenism (hirsutism), and obesity. Since the tubal patency is confirmed and the male factor is ruled out, the primary cause of infertility is anovulation due to PCOS.

Option C (Letrozole): According to SOGC Clinical Practice Guidelines, Letrozole is the recommended first-line ovulation induction agent for women with PCOS. It is associated with higher ovulation rates and live birth rates compared to clomiphene citrate in this population.
Option B (Clomiphene citrate): While historically the first-line, it is now considered second-line to letrozole for PCOS due to letrozole’s superior efficacy and lower risk of multiple gestations.
Option A (Metformin): While used in PCOS for metabolic indications, it is less effective than letrozole or clomiphene for live birth rates when used as a sole agent for infertility.
Option D (Gonadotropins): These are second-line or third-line agents used after failure of oral agents due to high cost and risk of Ovarian Hyperstimulation Syndrome (OHSS) and multiples.
Option E (OCPs): These would prevent pregnancy and are used for managing PCOS symptoms (hirsutism, irregular bleeding) in women not pursuing fertility.

Canadian Guidelines

For MCCQE1, familiarity with the following guidelines is essential:

SOGC (Society of Obstetricians and Gynaecologists of Canada):
- Ovulation Induction in WHO Group 2 Anovulation (2018): Establishes Letrozole as first-line.
- Advanced Reproductive Technologies: Guidelines on single embryo transfer (SET) to reduce multiple gestations.
CFAS (Canadian Fertility and Andrology Society):
- Provides clinical practice guidelines for ART laboratories and clinical management in Canada.
Public Health Agency of Canada:
- Recommendations on folic acid supplementation for low-risk vs. high-risk women.

References

Society of Obstetricians and Gynaecologists of Canada (SOGC). (2018). Ovulation Induction in WHO Group 2 Anovulation. J Obstet Gynaecol Can.
Medical Council of Canada. (2023). MCCQE Part I Objectives: Infertility.
Vause, T., et al. (2019). Image-guided hysterosalpingography: contrast agents and methodology. SOGC Clinical Practice Guideline.
Canadian Fertility and Andrology Society (CFAS). Clinical Practice Guidelines.
Uptodate. Overview of infertility. Accessed for general medical consensus.

Disclaimer: This content is for educational purposes for medical students preparing for the MCCQE1. Always consult the most recent clinical guidelines.