GC117 I Want To Have A Baby Male And Female Infertility
Male and female infertility refers to the inability of a couple to achieve pregnancy after 12 months of regular unprotected intercourse, resulting from disorders of sperm production or function, ovulatory dysfunction, tubal damage, uterine abnormalities, or unexplained factors in either partner.
I Want to Have a Baby: Male and Female Infertility
This lecture, delivered by Professor Ernest Hung Yu NG (Department of O&G, HKU), is a cornerstone General Clerkship session on reproductive medicine. It covers the entire clinical pathway from understanding normal fertility, through identifying causes of infertility in both sexes, to systematic investigation and evidence-based treatment including assisted reproductive technologies (ART). The lecture directly maps to summative exam questions on definitions, investigation thresholds, ovulation induction pharmacology, IVF procedures, and ethical dimensions of fertility treatment.
- Understand normal fertility (sperm journey, ovulation, fertilization, implantation)
- Know the causes of infertility (male, female, unexplained)
- Systematic investigations for infertility
- Treatment options including medical, surgical, and ART
Why this matters clinically: Infertility affects 10–15% of couples. A GP or O&G clinician must be able to take a focused history, order the three core investigations (semen analysis, serum progesterone, tubal patency test), provide pre-pregnancy advice, and know when to refer early. Understanding the principles of IVF/ICSI is essential for counselling.
1. Normal Fertility
Millions of sperm at coitus → 1% reach endocervical canal → a few thousand in Fallopian tube [1]
Why such attrition? The female reproductive tract acts as a biological filter. The acidic vaginal pH kills most sperm; cervical mucus selectively allows motile sperm with normal morphology; the uterotubal junction further selects. Only a few hundred reach the ampulla of the Fallopian tube where fertilization occurs. This is why even modest reductions in sperm count/motility can dramatically reduce fertility.
Normal fertility in women involves follicle development → ovulation → fertilization in the Fallopian tube → embryo implantation in the endometrium [1]
- Follicular phase: FSH recruits a cohort of follicles; one becomes dominant, producing rising oestradiol
- Ovulation: LH surge triggers follicular rupture ~36 hours later
- Luteal phase: Corpus luteum produces progesterone, preparing the endometrium
- Fertilization window: Oocyte viable ~12–24 hours; sperm viable ~3–5 days → fertile window is approximately 6 days ending on the day of ovulation
Peak monthly pregnancy rate ~25–30%; cumulative rate at 1 year ~80%; at 2 years ~90% [1]
High Yield - Pregnancy Rates
These numbers are crucial for interpreting ART success rates. If natural conception gives 80% at 1 year, then any ART must be compared against this baseline. A treatment giving 30% per cycle sounds impressive until you realize natural rates are 25–30%/month. This is why "cumulative pregnancy rate" matters more than per-cycle rates.
Definition 1: A disease characterized by failure to establish a clinical pregnancy after 12 months of regular unprotected sexual intercourse (International Glossary 2017) [1]
Definition 2: Failure to achieve pregnancy within 12 months in women < 35 years OR within 6 months in women > 35 years (ACOG/ASRM 2019) [1]
10–15% of couples affected [1]
Why the age distinction? Ovarian reserve declines steeply after age 35. Fecundability (monthly probability of conception) drops from ~25% at age 25 to ~10% at age 40. Waiting 12 months in a 38-year-old wastes precious reproductive time, so the threshold for investigation is halved to 6 months.
Both women and men can be affected. Multiple factors are common. [1]
| Category | Approximate % | Examples |
|---|---|---|
| Male factors | 30% | Production defects (idiopathic, endocrine, trauma, genetic); obstructive (absent vas, vasectomy); coital problems |
| Ovulatory dysfunction | 15% | PCOS, hypothalamic amenorrhoea, hyperprolactinaemia, ovarian insufficiency |
| Tubal factors | 20% | PID, endometriosis, previous surgery, ectopic |
| Endometriosis | 25% | Distorted anatomy, inflammatory peritoneal environment |
| Cervical/immunological/coital | Uncommon | Antisperm antibodies, vaginismus |
| Unexplained | By exclusion | Ovulation confirmed + patent tubes + normal semen |
Exam Framing - Five Important Causes
The five important causes per the lecture: (1) Ovulatory dysfunction/anovulation, (2) Tubal problems, (3) Endometriosis, (4) Male factors, (5) Unexplained [1]. This is the framework examiners expect you to use when listing causes.
4. History and Examination
Female: Age, menstrual cycle regularity (21–35 days), history of pelvic infection or surgery, previous investigations and treatment [1]
Male: Age/occupation, past health, coital history, smoking/alcohol [1]
Why each element matters:
- Age of the woman is the single most important prognostic factor (declining oocyte quality and quantity)
- Menstrual regularity (21–35 days) suggests 95% chance of ovulation [1] — this is a key teaching point
- Pelvic infection/surgery → tubal damage risk
- Coital history → frequency, timing, erectile dysfunction (a commonly overlooked cause)
- Smoking → reduces ovarian reserve in women, impairs sperm quality in men
- Occupation (male) → exposure to heat, chemicals, radiation
Female: Body weight, vaginal examination (uterine size, mobility, adnexal mass) [1]
Male: Testicular size, vas and epididymis, varicocele (? Necessary = the slide questions whether male exam is always needed) [1]
Why body weight? Obesity causes anovulation via excess peripheral oestrogen conversion (aromatase in adipose tissue) and insulin resistance → hyperandrogenism. BMI > 30 significantly reduces IVF success. Conversely, BMI < 18.5 causes hypothalamic amenorrhoea.
5. Investigations
5.1 Semen Analysis
2–3 samples after 2–7 days of sexual abstinence. WHO criteria. Low predictive values. [1]
Why 2–3 samples? Semen parameters vary considerably between ejaculates. A single abnormal result may be due to recent illness, stress, or abstinence duration. Two abnormal samples are needed before diagnosing male factor infertility.
Why 2–7 days abstinence? Too short (under 2 days) → low volume and count. Too long (over 7 days) → increased proportion of dead/immotile sperm and decreased motility.
Reference group: fertile men whose partners (regular cycles, bilateral patent tubes) got pregnant within 12 months. 5th centile used as lower reference values. [1]
| Parameter | 5th Edition | 6th Edition |
|---|---|---|
| Semen volume (mL) | 1.5 | 1.4 |
| Concentration (×10⁶/mL) | 15 | 16 |
| Total sperm number (×10⁶) | 39 | 39 |
| Total motility (%) | 40 | 42 |
| Progressive motility (%) | 32 | 30 |
| Morphology (%) | 4 | 4 |
Critical Exam Point - Semen Analysis Overlap
Extensive overlap exists between fertile and infertile men. None of the semen parameters is diagnostic of infertility. [1] The study by Guzick et al. (NEJM 2001) showed: Fertile men had mean concentration 67±50 vs infertile 52±42; motility 54±13 vs 49±15; morphology 14±5 vs 11±6. The distributions overlap massively. This means a man with "abnormal" WHO values may still be fertile, and vice versa. Semen analysis is a screening test, not a diagnostic test.
Sperm concentration threshold for natural conception: A WHO contraceptive study showed that when sperm concentration dropped below 3 million/mL through testosterone-induced suppression, contraceptive efficacy was achieved [1]. This gives us a pragmatic lower limit: below ~3M/mL, natural conception is very unlikely.
| Term | Definition |
|---|---|
| Oligozoospermia | Sperm concentration < 16M/mL (6th ed) |
| Asthenozoospermia | Total motility < 42% |
| Teratozoospermia | Normal morphology < 4% |
| Azoospermia | No sperm in ejaculate |
| Oligoasthenoteratozoospermia (OAT) | All three abnormal |
5.2 Causes of Male Infertility
Three categories: (1) Disorders of testicular control, (2) Obstructive disorders, (3) Primary testicular disorders [1]
| Category | Causes | Key Details |
|---|---|---|
| Disorders of testicular control | Hypogonadotrophic hypogonadism, Hyperprolactinaemia | Low FSH/LH → low testosterone → impaired spermatogenesis. Treatable with gonadotrophins or GnRH pulsatile therapy |
| Obstructive disorders | Infections, Congenital absence of vas deferens (CBAVD), Vasectomy | CBAVD associated with CF carrier status (CFTR mutations) [5]. Normal FSH, normal testicular size, azoospermia |
| Primary testicular disorders | Klinefelter syndrome (47,XXY), Varicocele, Infections (mumps), Trauma, Cryptorchidism, Radiotherapy/chemotherapy, Chronic illness | Klinefelter's: small firm testes, tall stature, gynaecomastia, azoospermia, elevated FSH [3][6] |
Y chromosome microdeletions: 3 deletion regions (AZFa, AZFb, AZFc) on Yq11 linked with male infertility. Different regions affect distinct phases of spermatogenesis. No sperms found in AZFa and AZFb deletions. [1]
Clinical significance:
- AZFa deletion → Sertoli cell-only syndrome → complete absence of germ cells → azoospermia → NO sperm retrieval possible
- AZFb deletion → maturation arrest → azoospermia → NO sperm retrieval possible
- AZFc deletion → variable phenotype, some sperm may be found → TESE may retrieve sperm for ICSI
Exam Trap
If asked about prognosis of Y microdeletion, remember that AZFa and AZFb deletions have the worst prognosis (no sperm retrieval possible), while AZFc may still allow sperm extraction. Also, if ICSI is used with AZFc sperm, male offspring will inherit the deletion and be infertile too — important for genetic counselling.
1. Hormonal assays: FSH, prolactin, testosterone 2. Karyotype and Y microdeletion for testicular failure 3. Vasogram 4. Testicular biopsy: not as routine; may be of prognostic value [1]
Interpretation framework:
| Finding | FSH | Testosterone | Diagnosis | Action |
|---|---|---|---|---|
| Azoospermia + small testes | High | Low | Primary testicular failure | Karyotype + Y microdeletion |
| Azoospermia + normal testes | Normal | Normal | Obstructive | Vasogram + consider MESA/TESE |
| Oligospermia + low FSH | Low | Low | Hypogonadotrophic hypogonadism | MRI pituitary, gonadotrophin Rx |
| Any + high prolactin | Variable | Low | Hyperprolactinaemia | MRI pituitary, dopamine agonist |
Serum mid-luteal progesterone levels (a week before next expected period) [1]
For irregular cycles: FSH, prolactin, thyroxine, USS ovarian morphology (PCO) [1]
For regular cycles: prolactin or thyroxine NOT indicated [1]
High Yield - Tests of Ovulation
Gold standard of ovulation is pregnancy. Other tests are inferential. Regular cycles (21–35 days) suggest 95% chance of ovulation. [1]
Serum progesterone: taken mid-luteal phase (~1 week before expected next period). > 3 ng/mL or > 10 nmol/L = presumptive evidence of recent ovulation. Levels fluctuate by sevenfold over a few hours. Not to assess quality of luteal phase. [1]
Why mid-luteal? Progesterone is secreted by the corpus luteum ONLY after ovulation. Its peak is approximately 7 days post-ovulation (= mid-luteal). If sampled too early or too late, you'll get a falsely low value. In a 28-day cycle, sample on day 21. In a 35-day cycle, sample on day 28.
Other Tests of Ovulation
| Test | How It Works | Limitations |
|---|---|---|
| Basal Body Temperature (BBT) | Progesterone causes ~0.3–0.5°F rise post-ovulation; BBT nadir suggests ovulation | Not accurate: ovulation can occur 6 days before to 4 days after nadir. Difficult to interpret. Not useful for timing intercourse. [1] |
| Urinary LH kits | Detect LH surge ~24–36 hours before ovulation. Peak conception probability is the day before and day of ovulation | Useful for timing intercourse; false negatives with dilute urine |
| Pelvic ultrasound | Progressive follicular growth → sudden collapse of pre-ovulatory follicle → internal echoes in corpus luteum → increase in cul-de-sac fluid [1] | Labour intensive; requires repeated scanning [1] |
| Endometrial biopsy | Secretory changes confirm ovulation | Invasive; NOT routinely recommended (ACOG 2019) [1] |
Hypothalamic: weight change (obesity, anorexia nervosa), drugs (tranquillizers), psychological disturbance [1]
Pituitary: tumours, Sheehan's syndrome, hyperprolactinaemia [1]
Ovary: ovarian insufficiency (chromosomal - Turner Syndrome, surgery, radiotherapy, chemotherapy, mumps), PCOS [1]
Other endocrine: thyroid disorders, adrenal disorders [1]
Investigation of Anovulation
High FSH ( > 25 IU/L) indicates ovarian insufficiency [1]
Check prolactin for pituitary causes [1]
Check for PCOS (USS), thyroid (TFT), Cushing's [1]
From first principles: FSH is high in ovarian insufficiency because of the loss of negative feedback from oestradiol and inhibin B. The pituitary "shouts louder" (high FSH) trying to stimulate non-responsive ovaries. Conversely, in hypothalamic/pituitary causes, FSH is low or inappropriately normal despite low oestrogen.
Two main methods: Hysterosalpingogram (HSG) and Laparoscopy [1]
| Feature | HSG | Laparoscopy |
|---|---|---|
| Invasiveness | Less invasive, outpatient | Operative, requires GA |
| Uterine cavity assessment | Can assess | Limited |
| Accuracy | Lower; false +ve due to proximal tubal spasm | More accurate |
| Peritubal adhesions | Not detected | Can visualize and treat |
| Endometriosis assessment | No | Can assess and treat |
| Complications | 4–5% PID after HSG | Surgical risks |
| When to use | Women with no comorbidities (no previous PID, ectopic, or clinical endometriosis) | Women thought to have comorbidities |
Hysterosalpingo-contrast-ultrasonography (HyCoSy) may be an alternative to HSG [1]
Hydrosalpinx (shown on lecture slides): A blocked, fluid-filled Fallopian tube. Important because hydrosalpinx fluid is embryotoxic and reduces IVF success rates. Current practice: salpingectomy or proximal tubal occlusion before IVF if hydrosalpinx is present.
Laparoscopy for unexplained infertility, advanced sperm function testing (DNA fragmentation), postcoital testing, thrombophilia testing, immunologic testing, karyotype, endometrial biopsy, prolactin (in regular cycles) — NOT routine (ACOG 2019) [1]
Exam Trap - What NOT to Order
Examiners love to test what you should NOT do. Post-coital test (PCT) was historically popular but has been abandoned — poor reproducibility and no correlation with pregnancy outcomes. Endometrial biopsy for "luteal phase defect" is also obsolete. Don't order karyotype unless indicated (testicular failure, recurrent miscarriage). Don't check prolactin in a woman with regular cycles.
6. Pre-Pregnancy Advice
Stop smoking, avoid excessive alcohol [1]
Men with poor quality sperm advised to wear loose fitting underwear and trousers, and avoid occupational or social situations that might cause testicular hyperthermia [1]
Why loose underwear? Spermatogenesis requires a temperature 2–4°C below core body temperature — this is why testes are external. Tight clothing, prolonged sitting, hot baths, and laptop use on the lap increase scrotal temperature and impair sperm production.
7. Treatment
7.1 Ovulation Induction
Aim: development of a single follicle [1]
High Prolactin → Bromocriptine/Cabergoline Normal FSH + Anovulation (PCOS/Hypothalamic) → Optimize weight → Drugs → Surgery High FSH → Ovarian insufficiency → Donor eggs [1]
First-line oral therapy in PCOS. Aromatase inhibitor. 2.5–7.5 mg/day for 5 days. Ovulation and pregnancy rates higher than clomid. Less multiple pregnancy compared with clomid. [1]
Mechanism from first principles: Letrozole inhibits aromatase → blocks conversion of androgens to oestrogens → reduced oestrogen negative feedback on hypothalamus/pituitary → increased FSH secretion → follicular development. Because the aromatase inhibition is reversible and short-lived, typically only one dominant follicle develops (less risk of multiples vs clomid).
Anti-oestrogen acting at hypothalamus. 50–150 mg/day for 5 days; up to 6 cycles. Ovulation rate 50–80%. Pregnancy rate 30–50%. [1]
Side effects: hot flushes, multiple pregnancy, ovarian cysts, abdominal distension/pain, blurring of vision [1]
Mechanism: Clomiphene blocks oestrogen receptors at the hypothalamus → hypothalamus "thinks" oestrogen is low → increases GnRH → increases FSH/LH → follicular development. Unlike letrozole, clomiphene has a long half-life (5–7 days) and its anti-oestrogenic effect on cervical mucus and endometrium may paradoxically reduce pregnancy rates despite inducing ovulation.
Letrozole vs Clomiphene - Exam Discriminator
| Feature | Letrozole | Clomiphene |
|---|---|---|
| Mechanism | Aromatase inhibitor | Anti-oestrogen at hypothalamus |
| Current status | First-line for PCOS | Second-line |
| Ovulation/pregnancy rate | Higher | Lower |
| Multiple pregnancy risk | Lower | Higher |
| Effect on endometrium | Neutral/positive | Anti-oestrogenic (thin endometrium) |
| Effect on cervical mucus | Neutral | Anti-oestrogenic (hostile mucus) |
FSH & LH or recombinant FSH injections. Acts directly on ovaries — very effective. Risk of OHSS and multiple pregnancy HIGH. Requires careful monitoring. [1]
Multiple pregnancies up to 40–50%!! [1]
Ovarian Hyperstimulation Syndrome (OHSS): 1–5%, life-threatening condition [1]
OHSS explained from first principles: Excessive ovarian stimulation → multiple follicles develop → massive oestrogen and VEGF production → increased vascular permeability → third-space fluid shifts (ascites, pleural effusions) → haemoconcentration → thromboembolism risk. Severe OHSS can cause renal failure, ARDS, and death. This is why gonadotrophin therapy requires ultrasound monitoring and dose titration.
Dopamine agonist useful in patients with hyperprolactinaemia. Ovulation rate > 90%. Pregnancy rate 80%. Side effects: nausea, postural hypotension. [1]
Why it works: Prolactin inhibits GnRH → reduced FSH/LH → anovulation. By suppressing prolactin with a dopamine agonist, GnRH pulsatility is restored → normal ovulation resumes. Cabergoline (longer-acting, fewer side effects) is often preferred in practice but the lecture names bromocriptine.
Surgical option for PCOS [1]
Laparoscopic ovarian drilling uses diathermy to puncture the ovarian capsule at multiple points. This reduces androgen-producing stroma and often restores ovulatory cycles. It's a second-line option when medical therapy fails.
Medical treatment is NOT effective. Oocyte donation: oocyte from donor, fertilized by husband's sperm, embryo transferred to recipient's uterus. [1]
Options: Tubal surgery vs IVF. Decision depends on: (1) The lesions, (2) The infertile couple, (3) The medical service [1]
Tubal surgery: microsurgical technique, laparotomy or laparoscopy. Types: adhesiolysis, re-anastomosis, salpingostomy [1]
When to choose surgery vs IVF:
- Mild distal tubal disease → surgery may be reasonable (cumulative pregnancy rate over multiple cycles)
- Severe tubal disease/bilateral hydrosalpinx → IVF preferred
- Reversal of sterilization → surgery if ≥4 cm of healthy tube remains
- Older woman or additional male factor → go straight to IVF
7.3 Male Factor Treatment
Effective medical treatments: Varicocele treatment, Vasectomy reversal, Gonadotrophins/GnRH for hypogonadotrophic hypogonadism, Bromocriptine for sexual dysfunction with hyperprolactinaemia [1]
If medical treatment not applicable: Ovarian stimulation + IUI, or IVF with conventional insemination or ICSI [1]
Ejaculated sperm, Epididymal sperm (MESA — Microsurgical Epididymal Sperm Aspiration), Testicular sperm (TESE — Testicular Sperm Extraction) [1]
When to use each:
- Ejaculated → first choice if any motile sperm present
- MESA → obstructive azoospermia (e.g., CBAVD, failed vasectomy reversal)
- TESE → non-obstructive azoospermia (may find focal spermatogenesis in testicular tissue)
Anti-oestrogens, androgens, bromocriptine, and kinin-enhancing drugs for abnormal semen quality — NOT effective. Antioxidants, mast cell blockers, alpha-blockers need further evaluation. Systemic corticosteroids for antisperm antibodies — NOT recommended. [1]
Exam Trap - Empirical Male Infertility Treatment
Do NOT recommend testosterone/androgens for male infertility with abnormal semen. Exogenous testosterone actually SUPPRESSES spermatogenesis via negative feedback on FSH/LH. This is a common misconception and exam trap.
Minimal/mild endometriosis: Medical treatment does NOT enhance fertility. Surgical ablation (diathermy or laser) IMPROVES fertility. Ovarian stimulation + IUI. IVF. [1]
Why medical treatment doesn't work for endometriosis-related infertility: GnRH agonists, progestins, and danazol suppress endometriosis but also suppress ovulation. You can't conceive while taking them, and recurrence after stopping is high. Surgery removes/destroys implants and restores anatomy, giving a window of improved fertility.
Expectant treatment recommended. Clomid NOT recommended. Unstimulated IUI NOT recommended. CC + unstimulated IUI unlikely to offer superior live birth rates compared with expectant management (Bhattacharya et al., 2008). IVF offered for persistent unexplained infertility. [1]
High Yield - Unexplained Infertility Management
This is a commonly tested discriminator. Students instinctively want to "do something" for unexplained infertility, but the evidence shows that clomiphene and unstimulated IUI do NOT improve outcomes over expectant management. The correct answer is: expectant management first, then IVF if pregnancy doesn't occur.
Investigate cause and treat: psychotherapy, drugs for erectile dysfunction (e.g., Viagra). IUI by husband's sperm at time of ovulation. [1]
Sexual dysfunction and infertility overlap: Studies show 32.5% of subfertile women attending fertility clinics have sexual dysfunction [8]. Infrequent coitus → reduced exposure to sperm → infertility. Always ask about coital frequency and sexual function as part of fertility assessment.
Increases motile sperm in uterus through IUI around ovulation. Ovarian stimulation increases oocytes available. Pregnancy rate ~10% per cycle. [1]
How IUI works: Semen is washed and prepared (removing prostaglandins, debris, immotile sperm) → concentrated motile sperm injected directly into the uterine cavity via a catheter → bypasses cervical barrier. Combined with ovarian stimulation (usually gonadotrophins) to increase target oocytes.
7.8 In Vitro Fertilization (IVF)
1. Stimulation of ovaries, 2. Oocyte pickup, 3. Fertilization, 4. Embryo transfer [1]
Period → Ovarian stimulation (gonadotrophins) → GnRH agonist or antagonist to prevent premature LH surge → Egg retrieval → Embryo transfer → Pregnancy test [1]
Why suppress endogenous LH? Without suppression, the developing follicles could trigger a premature LH surge → premature ovulation → missed oocyte retrieval. GnRH agonists (after initial flare) or antagonists prevent this.
1. Conventional insemination: oocytes placed in culture medium with prepared sperm 2. Intracytoplasmic sperm injection (ICSI): injecting a single sperm directly into an oocyte [1]
When to use ICSI over conventional:
- Severe male factor (very low count/motility)
- Surgically retrieved sperm (MESA/TESE)
- Previous fertilization failure with conventional IVF
- Low oocyte yield
Day 0 (retrieval) → Day 1 (fertilization check) → Day 2–3 (cleavage stage embryo) → Day 5–6 (blastocyst) [1]
Replace ONE embryo to reduce risk of multiple pregnancies. Replace TWO embryos if: ≥38 years at IVF OR not pregnant after 2 IVF cycles AND no previous livebirth. [1]
Single vs Double Embryo Transfer - HKU Policy
The default is single embryo transfer (SET) to minimize multiple pregnancy risk (which carries risks of prematurity, pre-eclampsia, and perinatal morbidity). Double embryo transfer is reserved for older women or those with poor prognosis. This is a commonly tested counselling point.
The lecture shows a cumulative live birth curve for the first IVF cycle. Key points:
- Per-cycle live birth rate is approximately 30–40% in women < 35, declining with age
- Cumulative rate improves with frozen embryo transfers from the same stimulation cycle
- Age of the woman is the strongest predictor of IVF success
9. Integration with Related Material
The 2020 SAQ tested surrogacy ethics [9]:
- Gestational surrogacy (embryo implanted in surrogate who has no genetic relationship) vs traditional surrogacy (surrogate's own oocyte)
- Ethical challenges: commodification of reproduction, exploitation of surrogates, legal parentage, psychological impact on surrogate/child, consent issues
- Arguments supporting: reproductive autonomy, fulfilling desire for genetically related child
The 2022 SAQ tested oocyte freezing and donor sperm ethics [10]:
- Storage duration of oocytes in HK: 10 years (extendable under certain conditions)
- Ethical concerns: welfare of the unborn child, social vs medical egg freezing, single parenthood
- Donor sperm ethical objections: anonymity issues, commodification, welfare of child, right to know genetic origin
Hyperprolactinaemia [3][4][7]: Prolactin inhibits GnRH → hypogonadotrophic hypogonadism → anovulation in women, impotence/infertility in men. Causes include prolactinoma, drugs (antipsychotics, antiemetics), hypothyroidism (↑TRH). Treatment: dopamine agonists (bromocriptine, cabergoline).
Turner Syndrome (45,X) [6]: Ovarian dysgenesis → primary ovarian insufficiency → high FSH, streak gonads. Pregnancy only possible with donor oocyte IVF.
Klinefelter Syndrome (47,XXY) [3]: Small firm testes, azoospermia, tall stature, gynaecomastia. High FSH, low testosterone. Micro-TESE may rarely retrieve sperm for ICSI.
10. Likely Exam Questions
Q1: A 32-year-old woman and her 35-year-old husband have been trying to conceive for 14 months. She has regular 28-day cycles. List three initial investigations you would order.
Markscheme: (1) Semen analysis ×2–3 after 2–7 days abstinence; (2) Mid-luteal serum progesterone (day 21 in a 28-day cycle, > 10 nmol/L confirms ovulation); (3) HSG (no risk factors) or laparoscopy (if risk factors for tubal disease/endometriosis)
Q2: A woman with PCOS and BMI 34 wants to conceive. Outline the stepwise management.
Markscheme: (1) Lifestyle modification: weight reduction, folic acid 0.4mg, stop smoking/alcohol; (2) First-line: letrozole 2.5–7.5 mg/day ×5 days; (3) Second-line: clomiphene citrate or gonadotrophins (with monitoring); (4) Third-line: laparoscopic ovarian drilling; (5) If still unsuccessful: IVF
Q3: Explain why exogenous testosterone should NOT be given to treat male infertility with oligospermia.
Markscheme: Exogenous testosterone suppresses hypothalamic-pituitary axis via negative feedback → decreased FSH and LH secretion → decreased intratesticular testosterone → impaired spermatogenesis → worsened sperm count. It acts as a male contraceptive.
Q4: A couple with unexplained infertility asks about clomiphene. What do you advise?
Markscheme: Clomiphene NOT recommended for unexplained infertility. CC + unstimulated IUI is unlikely to offer superior live birth rates compared with expectant management (Bhattacharya et al., 2008). Recommend expectant management first, then IVF if unsuccessful.
| Trap | Why Students Get It Wrong |
|---|---|
| Ordering prolactin in a woman with regular cycles | Regular cycles suggest 95% ovulation — prolactin not indicated unless cycles are irregular |
| Ordering postcoital test | Obsolete investigation; ACOG 2019 says NOT routine |
| Recommending testosterone for male infertility | Testosterone suppresses spermatogenesis |
| Saying letrozole is second-line for PCOS | Letrozole is FIRST-line (above clomiphene) per current evidence and this lecture |
| AZFa deletion → recommend TESE | AZFa and AZFb deletions: NO sperm retrieval possible. Only AZFc may allow TESE |
High Yield Summary
Definition: Infertility = failure to conceive after 12 months regular unprotected intercourse (< 35 years) or 6 months ( > 35 years). Affects 10–15% of couples.
Five causes: Ovulatory dysfunction, tubal factors, endometriosis, male factors, unexplained.
Three core investigations: (1) Semen analysis (WHO 5th centile values), (2) Mid-luteal progesterone ( > 10 nmol/L = ovulation), (3) HSG or laparoscopy for tubal patency.
Ovulation induction: Letrozole (1st line for PCOS) > Clomiphene > Gonadotrophins > Ovarian drilling. Bromocriptine for hyperprolactinaemia. Donor oocytes for ovarian insufficiency.
Male factor: Gonadotrophins for hypogonadotrophic hypogonadism; vasectomy reversal for obstruction; IUI or IVF/ICSI for most cases. NEVER give testosterone for oligospermia.
Unexplained infertility: Expectant → IVF. Clomid and unstimulated IUI NOT recommended.
IVF: Ovarian stimulation → egg retrieval → conventional insemination or ICSI → embryo transfer (single embryo default; double only if ≥38 or failed 2 cycles).
Pre-pregnancy: Folic acid 0.4 mg, weight optimization, stop smoking/alcohol, loose underwear for men.
Age is the single most important prognostic factor. Refer early if > 35.
Active Recall - Infertility
[1] Lecture slides: GC 117. I want to have a baby male and female infertility.pdf (all pages) [2] Lecture slides: Block C - I want to have a baby_ male and female infertility.pdf (p1) [3] Senior notes: Block A - I keep on bumping into people on my side_ pituitary tumours; hypopituitarism.pdf (p21-22) [4] Senior notes: Ryan Ho Endocrine.pdf (p110) [5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p182) — CF and absent vas deferens [6] Senior notes: Adrian Lui Pediatrics Notes.pdf (p506) — Turner Syndrome [7] Senior notes: Ryan Ho Fundamentals.pdf (p443) [8] Lecture slides: MBBS_SRH_2025.8.10.pdf (p35) — Sexual dysfunction in subfertile women [9] Past papers: 2020 Fourth Summative SAQ.pdf (Q12) — Surrogacy ethics [10] Past papers: 2022 Fourth Summative SAQ.pdf (Q10) — Oocyte freezing and donor sperm [11] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1052) — Chlamydia and PID [12] Senior notes: Ryan Ho Urogenital.pdf (p241, p249) — STDs and infertility
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