How is infertility defined and what are the common causes?
Infertility is the failure to achieve pregnancy after 12 months or more of regular unprotected intercourse (WHO). Many guidelines start the evaluation after 6 months in women older than 35. Primary infertility means a pregnancy has never been achieved; secondary infertility means at least one earlier pregnancy occurred.
About 85% of couples conceive within 12 months of adequate intercourse, and the average monthly conception probability is roughly 15–20%. Worldwide about one in six people of reproductive age experience infertility. In about 50% of couples a female factor is responsible, in about 40% a male factor, and the rest have combined causes.
| Category | Share of cases | Examples |
|---|---|---|
| Ovulatory dysfunction | 25–40% | PCOS (about 70% of anovulation), hyperprolactinaemia, hypothalamic amenorrhoea, primary ovarian insufficiency, thyroid disease |
| Tubal factor | 20–35% | Pelvic inflammatory disease (chlamydia), endometriosis, previous pelvic surgery |
| Uterine factor | 10–15% | Fibroids, endometrial polyps, Asherman syndrome, septate uterus |
| Endometriosis | 10–15% | Adhesions, distorted anatomy, endometriomas lowering AMH |
| Unexplained | 15–30% | Normal results after a complete workup of both partners |
What do the history and examination add before any test?
A good history often points to the diagnosis before any investigation is ordered. The key questions and what they suggest are listed below.
| Finding | Suggests |
|---|---|
| Cycle variation more than 7 days, oligomenorrhoea | Ovulatory dysfunction; oligomenorrhoea occurs in about 80% of PCOS |
| Amenorrhoea | Hypothalamic dysfunction or primary ovarian insufficiency |
| Pelvic pain, dyspareunia | Endometriosis or PID |
| Galactorrhoea | Hyperprolactinaemia |
| Hirsutism, acne, obesity, acanthosis nigricans | PCOS and insulin resistance |
| BMI below 18.5 kg/m2 | Hypothalamic amenorrhoea |
| Short stature, webbed neck, widely spaced nipples, cubitus valgus | Turner syndrome |
| Previous miscarriage or ectopic pregnancy | Uterine or tubal pathology |
Lifestyle also matters: smoking is reported to reduce fertility by about 30%, and drinking more than 14 units of alcohol per week roughly doubles the risk of infertility. Fertility starts to fall after about 30, and falls more steeply after 35, because oocyte number and quality decline (aneuploidy rises from about 20% at 30 to about 60% at 40). For the physiology behind this, revise the menstrual cycle.
Which tests confirm ovulation and ovarian reserve?
Ovulation is confirmed by the luteal-phase progesterone rise. A mid-luteal serum progesterone above 3 ng/mL confirms ovulation. A mid-cycle rise of at least 0.5 °F in basal body temperature is suggestive but variable, and basal temperature charting is considered unreliable. Ovulation predictor kits detect the LH surge in urine.
| Test | Interpretation |
|---|---|
| AMH | Below 1 ng/mL low reserve; 1–3.5 ng/mL normal; above 4 ng/mL suggests PCOS |
| Antral follicle count (transvaginal ultrasound, follicles 9 mm or less) | Below 5 low reserve; 5–20 normal; above 20 may suggest PCOS |
| Day 3 FSH and oestradiol | FSH 3–9 mIU/mL is typical; above 10 means diminished reserve; below 3 suggests hypothalamic-pituitary dysfunction |
| TSH | Above 4 mIU/L suggests hypothyroidism, which can impair ovulation |
| Prolactin | Above 25 ng/mL indicates hyperprolactinaemia |
| 17-hydroxyprogesterone | Raised in congenital adrenal hyperplasia |
| Karyotype, fragile X premutation | Primary ovarian insufficiency work-up |
How is tubal patency assessed, and what is the role of HSG?
Hysterosalpingography (HSG) is the standard first test for tubal patency. Contrast is injected through the cervix under fluoroscopy; it fills the uterine cavity and, if the tubes are open, spills into the peritoneal cavity. HSG has 85–90% sensitivity for tubal obstruction. Studies show higher pregnancy and live-birth rates after HSG, particularly when oil-soluble contrast is used.
| Test | Notes |
|---|---|
| HSG | 85–90% sensitive for obstruction; shows uterine cavity and tubal outline |
| HyCoSy (hysterosalpingo-contrast sonography) | About 80% concordance with HSG; less invasive, no radiation |
| Laparoscopy | Gold-standard investigation for endometriosis; allows direct tubal assessment and treatment |
| Hysteroscopy | Diagnostic and therapeutic for intrauterine lesions |
Chlamydial PID is the typical cause of tubal damage. Roughly 15% of untreated chlamydial infections progress to tubal fibrosis, and hydrosalpinx fluid reduces implantation in IVF. This is why salpingectomy for hydrosalpinx before IVF improves success (about 20% in the StatPearls review) and lowers the risk of ectopic pregnancy. A damaged tube also raises the ectopic pregnancy risk.
How is the uterine cavity evaluated?
The uterine assessment looks for fibroids, polyps, adhesions and congenital anomalies. Transvaginal ultrasound is the first-line, non-invasive test; the other modalities add detail.
| Modality | Use | Reported performance |
|---|---|---|
| Transvaginal ultrasound | First-line for fibroids and adnexal masses | About 90% sensitivity for fibroids |
| Sonohysterography (saline infusion) | Endometrial cavity, polyps | About 95% sensitivity for polyps |
| Hysteroscopy | Direct view, with simultaneous treatment | Diagnostic and therapeutic |
| MRI | Complex congenital and acquired anomalies | About 98% accuracy |
- Submucosal fibroids distort the cavity and reduce endometrial receptivity; myomectomy is reported to improve implantation.
- Asherman syndrome (intrauterine adhesions) reduces pregnancy rates by about 70% in the StatPearls review.
- Septate uterus raises miscarriage risk; septum resection reduces miscarriage rates.
- Hysteroscopic surgery for intrauterine lesions improves pregnancy rates by about 50–70%.
What are the WHO reference values for semen analysis?
About 40% of infertility involves a male factor, so semen analysis is part of the first-line workup in every couple. A normal semen analysis effectively excludes male infertility, which lets the clinician focus on the female partner. Collection needs 3–7 days of abstinence, a clean wide-mouthed non-toxic container (no latex condoms) and delivery to the laboratory within 1 hour.
| Parameter | Lower reference limit |
|---|---|
| Volume | More than 1.5 mL |
| pH | More than 7.2 |
| Total sperm number | 39 million per ejaculate or more |
| Morphology | More than 4% normal forms (Tygerberg strict criteria) |
| Vitality | More than 58% live sperm |
| Progressive motility | More than 32% |
| Total motility (progressive plus non-progressive) | More than 40% |
| Agglutination | None |
- Low volume (under 1.5 mL, especially under 1 mL): check a post-ejaculation urine specimen for sperm to confirm retrograde ejaculation (diabetes, spinal cord injury, prostate surgery).
- Low volume with no sperm can indicate ejaculatory duct obstruction or congenital bilateral absence of the vas deferens.
- Abnormal results are repeated after about 3 months, the length of one spermatogenic cycle, unless the count is very low or absent. Revise spermatogenesis.
- Sperm count below 5 million/mL raises the possibility of Klinefelter syndrome or Y-chromosome microdeletion; a karyotype is advised.
How is female infertility treated, and which drug is used when?
Treatment is directed at the cause. In ovulatory dysfunction, drugs usually come first; tubal disease may need surgery or IVF; unexplained infertility often goes to IUI or IVF.
| Cause | Treatment | Points |
|---|---|---|
| PCOS with anovulation | Letrozole (preferred); clomiphene citrate; metformin adjunct | Letrozole gives higher live-birth rates than clomiphene in PCOS (27.5% vs 19.1%) and fewer multiple pregnancies |
| Weight above normal with PCOS | 5–10% weight loss | Restores ovulation in about 50–60% of obese women with PCOS |
| Hyperprolactinaemia | Cabergoline or bromocriptine | Restores ovulation in 80–90% |
| Ovulation induction failure | Gonadotropins (FSH, LH, hCG) | Ovulation in about 90%, OHSS risk 1–6% |
| Severe tubal disease | IVF | Live-birth rates 40–50% per cycle under age 35 |
| Hydrosalpinx | Salpingectomy before IVF | Removes toxic fluid, improves implantation |
| Unexplained | IUI with ovulation induction, then IVF | IUI 10–15% per cycle; IVF 30–40% |
| Septate uterus | Hysteroscopic septum resection | Reduces miscarriage |
| Endometriosis stage I–II | Laparoscopic excision | Raises pregnancy rate by about 50%; hormonal suppression alone does not improve fertility |
What is the stepwise approach, and which traps appear in exams?
- Define and start early: 12 months of regular unprotected intercourse; start sooner (6 months) above age 35 or when history suggests a cause.
- Both partners together: history, examination and a semen analysis for the man, since a normal result excludes the male factor.
- Ovulation: cycle history, mid-luteal progesterone, with TSH and prolactin in anovulatory women.
- Ovarian reserve in older women or when treatment is planned: AMH, antral follicle count, day 3 FSH.
- Tubes and cavity: HSG or HyCoSy, plus transvaginal ultrasound; hysteroscopy or laparoscopy when a lesion or endometriosis is suspected.
- Treat the cause, then move to IUI or IVF if the cause is unexplained or the tubes are damaged.
| Question | Trap | Answer |
|---|---|---|
| Test that confirms ovulation | Basal body temperature | Mid-luteal progesterone above 3 ng/mL |
| AMH above 4 ng/mL | Reading it as high reserve and good prognosis | Suggests PCOS |
| Day 3 FSH above 10 mIU/mL | Reading it as normal | Diminished ovarian reserve |
| First test for tubal patency | Laparoscopy | HSG (laparoscopy is gold standard for endometriosis) |
| Semen volume below 1.5 mL | Assuming a low count | Check for retrograde ejaculation with post-ejaculation urine |
| Preferred drug for ovulation induction in PCOS | Clomiphene | Letrozole |
| Does hormonal suppression help endometriosis infertility? | Assuming it helps | No; it relieves symptoms but does not improve fertility |