Infertility — Causes, Diagnosis, IVF & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Infertility is defined as failure to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse (or after 6 months in women over 35 — when earlier investigation is warranted). Primary infertility refers to couples who have never achieved a pregnancy; secondary infertility refers to inability to conceive again after one or more previous pregnancies. The WHO estimates that approximately 186 million people globally are affected by infertility, with 1 in 6 couples meeting the clinical definition at some point in their reproductive lives. Infertility has a male factor in approximately 50% of cases (either as the sole cause or contributing factor — highlighted by the importance of semen analysis as a first step), a female factor in approximately 40%, and unexplained infertility in 10-15% after full workup. Natural conception rates in the general population: approximately 84% of couples conceive within 1 year and 92% within 2 years of regular unprotected intercourse. Fertility declines significantly with age, particularly in women after 35 (ovarian reserve diminishes, oocyte quality decreases, and miscarriage risk increases). Advanced maternal age above 40 substantially reduces the chance of success with own-egg IVF (live birth rate drops to 5-10% per cycle above 43).

Female causes: ovulatory disorders (most common female cause — 25-30%): polycystic ovary syndrome (PCOS — accounts for 70-80% of anovulatory infertility), hypothalamic hypogonadism (low body weight, excessive exercise, stress), hyperprolactinaemia, primary ovarian insufficiency (POI — premature menopause below age 40), and thyroid dysfunction. Tubal factor (20-30%): fallopian tube damage from pelvic inflammatory disease (PID — most commonly from Chlamydia trachomatis — leading to hydrosalpinx and bilateral tubal occlusion); prior ectopic pregnancy; or endometriosis-related adhesions. Uterine and cervical factors: uterine fibroids (submucosal — distort the endometrial cavity), endometrial polyps, congenital uterine anomalies (bicornuate, septate uterus), intrauterine adhesions (Asherman's syndrome), and cervical stenosis. Endometriosis (affects fertility through endometriomas, adhesions, inflammatory cytokines, and impaired implantation). Diminished ovarian reserve: assessed by anti-Mullerian hormone (AMH) level and antral follicle count (AFC) — reduced in advanced age, after ovarian surgery, chemotherapy, or radiotherapy. Male causes: semen abnormalities (oligospermia — low sperm count; asthenospermia — reduced motility; teratospermia — abnormal morphology; azoospermia — absent sperm). Common causes: varicocele (most common correctable male infertility cause — present in 35% of men with primary infertility); testicular failure (Klinefelter's syndrome XXY — most common genetic cause; prior orchitis; chemotherapy; undescended testes); obstructive azoospermia (vas deferens obstruction from prior vasectomy, infection, cystic fibrosis — CFTR gene mutations); ejaculatory dysfunction; and Y-chromosome microdeletions (AZF region deletions). Lifestyle factors affecting both sexes: smoking (reduces sperm count and oocyte quality); obesity (disrupts the HPG axis and oocyte quality); excessive alcohol; anabolic steroids (suppress spermatogenesis profoundly); excessive heat exposure for men (laptop use, hot baths, occupational heat).

Infertility itself is defined by failure to conceive rather than by specific symptoms — many infertile couples have no symptoms other than inability to achieve pregnancy. However, certain associated features provide diagnostic clues. In women: irregular periods or absent periods (amenorrhoea) — suggesting ovulatory dysfunction (PCOS, hypothalamic hypogonadism, POI); heavy, painful periods and pelvic pain — suggesting endometriosis or fibroids; galactorrhoea (breast milk production) — hyperprolactinaemia; hirsutism and acne — PCOS and hyperandrogenism; and symptoms of thyroid disease. In men: small testes (may indicate testicular failure), varicocele (dilated varicosity in the spermatic cord — may cause scrotal discomfort or be asymptomatic), ejaculatory problems, prior history of mumps orchitis or cryptorchidism (undescended testis), and previous sexually transmitted infections. In both: recurrent miscarriage (pregnancy loss in 3 or more consecutive pregnancies) — associated with antiphospholipid syndrome, uterine anomalies, chromosomal translocations, and thrombophilias — represents a distinct subfertility problem requiring specialist evaluation. The emotional and psychological impact of infertility is significant: depression, anxiety, relationship strain, social isolation, and grief are common — psychological support should be integral to fertility care.

Investigations are best initiated for both partners simultaneously. Female investigations: day 2-5 FSH, LH, oestradiol, and AMH (ovarian reserve markers — AMH most reliable, not cycle-dependent); progesterone at day 21 (luteal phase — confirms ovulation — above 30 nmol/L indicates ovulation in a 28-day cycle); prolactin, TSH (thyroid), testosterone, DHEAS (if hyperandrogenaemia suspected); pelvic ultrasound (antral follicle count, ovarian morphology, endometrial thickness, uterine anatomy, and adnexal masses); hysterosalpingography (HSG) — contrast X-ray assessing tubal patency and uterine cavity; laparoscopy and dye test (gold standard for tubal assessment and diagnosis of endometriosis and adhesions — usually performed when HSG is abnormal or other factors suggest peritoneal disease); hysteroscopy (direct visualisation of the uterine cavity). Male investigations: semen analysis (volume, pH, sperm concentration, total count, motility, morphology — WHO 2021 reference values: concentration above 16 million/mL, progressive motility above 30%, normal morphology above 4%); if abnormal: repeat semen analysis after 3 months; FSH, LH, testosterone (to assess testicular function); karyotype and Y-chromosome microdeletion analysis (for azoospermia/severe oligospermia); CFTR mutation testing (obstructive azoospermia); scrotal ultrasound (varicocele, testicular mass). Unexplained infertility is diagnosed when both partners have normal fertility investigations.

Ovulation induction for PCOS and anovulatory infertility: letrozole (aromatase inhibitor — 2.5-7.5 mg days 3-7 of cycle) — superior to clomiphene (50-150 mg days 2-6) for PCOS (higher live birth rates, lower multiple pregnancy rates — preferred first-line per NICE and ASRM 2023 guidelines); if oral agents fail, injectable gonadotrophins (FSH) with careful monitoring (ultrasound — follicle tracking) to minimise multiple pregnancy risk and ovarian hyperstimulation syndrome (OHSS). Metformin in PCOS: improves ovulation rates and reduces OHSS risk in combination with gonadotrophins; reduces androgen levels and improves insulin sensitivity. Weight loss (5-10% body weight reduction in overweight women with PCOS) often restores ovulation and significantly improves fertility. Intrauterine insemination (IUI): prepared washed sperm placed directly into the uterus at the time of ovulation (natural or stimulated cycle); effective for cervical factor and mild male factor infertility; commonly used in unexplained infertility — 3-6 cycles before proceeding to IVF. In vitro fertilisation (IVF): oocytes retrieved after ovarian stimulation combined with sperm in the laboratory; embryos cultured for 3-5 days; one or two embryos transferred to the uterus. IVF success rates by age: approximately 32-40% live birth rate per cycle below 35; 15-20% at 38-40; 5-10% above 43. Intracytoplasmic sperm injection (ICSI): single sperm injected directly into an egg — used for severe male factor infertility, failed fertilisation in prior IVF, or surgically retrieved sperm (testicular sperm extraction, TESE, for azoospermia). Preimplantation genetic testing for aneuploidy (PGT-A): screens embryos for chromosomal abnormalities before transfer — evidence for improved live birth rates in selected populations. Donor eggs: used when diminished ovarian reserve is severe or in POI — significantly improves live birth rates for older women. Surgical treatments: laparoscopic surgery for endometriosis (improves spontaneous and IVF conception rates), varicocele ligation (surgery or embolisation — improves sperm parameters in selected men).

Infertility and its treatments carry significant medical, psychological, and social complications. Psychological impact: infertility is consistently rated among the most stressful life events — depression and anxiety affect 40–50% of women undergoing fertility treatment; social isolation, relationship strain, grief for unachieved parenthood, and loss of sexual spontaneity are common consequences; psychological counselling support should be proactively offered during all stages of treatment. Ovarian hyperstimulation syndrome (OHSS): a potentially serious complication of gonadotrophin stimulation occurring in 1–5% of IVF cycles; mild OHSS (bloating, pelvic discomfort) is common; severe OHSS (ascites, pleural effusion, haemoconcentration, thromboembolism, renal impairment) requires hospitalisation, IV fluids, and anticoagulation — GnRH antagonist protocols and GnRH agonist trigger significantly reduce severe OHSS risk. Multiple pregnancy: the most significant obstetric complication of ART — twin and higher-order pregnancies increase risk of preterm birth (50% of twins deliver before 37 weeks), low birth weight, cerebral palsy, maternal pre-eclampsia, gestational diabetes, PPH, and NICU admission; single embryo transfer policies have substantially reduced multiple pregnancy rates. Ectopic pregnancy: occurs in 2–5% of IVF pregnancies (versus 1–2% in natural conception), due to underlying tubal pathology. Long-term complications of untreated underlying causes: PCOS causes metabolic syndrome and cardiovascular risk; premature ovarian insufficiency causes osteoporosis and cardiovascular disease from oestrogen deficiency; endometriosis progresses and may cause chronic pelvic pain and bowel or bladder complications. Surgical complications: ovarian drilling, laparoscopy, and hysteroscopy carry procedural risks of haemorrhage, infection, anaesthetic complications, and adhesion formation.

Prevention of infertility where possible: STI prevention (Chlamydia screening and treatment prevents tubal damage — the leading preventable cause of female infertility); avoid smoking (reduces oocyte quality and sperm parameters significantly); maintain healthy weight; limit alcohol (above 14 units per week in women and above 14 units per week in men impairs fertility); avoid anabolic steroids (profoundly suppresses spermatogenesis — often irreversible); manage chronic conditions (thyroid disease, diabetes, coeliac disease). Timing intercourse for maximum fertility: the fertile window spans approximately 6 days — the 5 days before ovulation and the day of ovulation; LH surge kits (ovulation predictor kits) identify the day before ovulation; basal body temperature charting can retrospectively confirm ovulation. Seek fertility evaluation earlier if: woman over 35 (investigate after 6 months, not 12); irregular periods; known PCOS, endometriosis, or uterine abnormality; prior pelvic inflammatory disease; prior cancer treatment; or male partner has known fertility risk factors (varicocele, prior testicular surgery, chemotherapy). Egg freezing (oocyte cryopreservation) — social or medical fertility preservation — allows women to defer family planning while storing eggs at younger age when quality is higher.

Seek evaluation from a GP or fertility specialist if: you have been trying to conceive for 12 months without success (or 6 months if aged over 35 — as fertility declines with age and earlier intervention improves outcomes); periods are irregular, absent, or very painful (suggesting ovulatory disorder or endometriosis); you have had a prior sexually transmitted infection that may have caused tubal damage; you have a history of pelvic surgery, endometriosis, uterine fibroids, or ovarian cysts; or your male partner has had prior testicular problems, surgery, or chemotherapy. Fertility evaluation is comprehensive and should investigate both partners simultaneously — semen analysis is a simple, non-invasive test that should always be among the first investigations. Both partners deserve thorough evaluation before proceeding to treatment. The emotional burden of infertility is substantial — seek psychological support (fertility counselling, support groups, psychotherapy) alongside medical treatment, as mental health significantly impacts treatment outcomes and quality of life.