Female Infertility — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Infertility is defined as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (or 6 months in women aged 35 or above). Female infertility encompasses a diverse range of conditions affecting ovulation, the fallopian tubes, the uterine cavity, or cervical function — each requiring different evaluation and treatment approaches. Female factors account for approximately 40% of all infertility, male factors for approximately 30-40%, and combined or unexplained factors for the remainder. Infertility affects an estimated 48 million couples and 186 million individuals globally. Advances in assisted reproductive technology (ART) — particularly IVF — have dramatically expanded treatment options over the past four decades, with over 8 million babies born via IVF since Louise Brown in 1978.

Ovulatory dysfunction (35% of female infertility): WHO Group 1 (hypothalamic-pituitary failure — amenorrhoea, low FSH/LH — anorexia, excessive exercise, functional hypothalamic amenorrhoea); WHO Group 2 (normogonadotrophic normo-oestrogenic anovulation — PCOS is most common cause, accounting for 80% of Group 2); WHO Group 3 (premature ovarian insufficiency — elevated FSH, low oestrogen). Tubal and peritoneal factors (30%): pelvic inflammatory disease (Chlamydia trachomatis is the most preventable cause — tubal blockage and hydrosalpinx), endometriosis (ectopic endometrial tissue causing adhesions, tubal occlusion, impaired oocyte quality), previous pelvic surgery, and ectopic pregnancy. Uterine factors (10%): submucosal fibroids (distorting the cavity), Asherman's syndrome (intrauterine adhesions after D&C), endometrial polyps, congenital uterine anomalies (septate uterus — most common clinically significant anomaly). Unexplained infertility (25%): all investigations normal — subtle defects in oocyte quality, fertilisation, or implantation are likely. Age-related decline in fertility: female fertility declines significantly after 35 and steeply after 40 (reduced oocyte quantity and quality — rising aneuploidy rates). Premature Ovarian Insufficiency (POI/POF): loss of ovarian function before 40.

Infertility itself — defined by failure to conceive — is the primary presenting concern rather than a specific symptom. Associated clinical features depend on the underlying cause: Irregular or absent periods (oligomenorrhoea or amenorrhoea) — suggests ovulatory dysfunction (PCOS, hypothalamic amenorrhoea, POI, thyroid disease, hyperprolactinaemia). Signs of PCOS: irregular periods, hirsutism (excess hair growth in androgen-dependent areas), acne, weight gain, acanthosis nigricans. Signs of premature ovarian insufficiency (POI): irregular or absent periods before 40, menopausal symptoms (hot flushes, night sweats, vaginal dryness, mood changes). Dysmenorrhoea (painful periods) and deep dyspareunia (pain during intercourse) suggest endometriosis. Previous pelvic infections, STIs, or pelvic surgery — risk for tubal damage. Galactorrhoea (nipple discharge) — hyperprolactinaemia. Thyroid symptoms — hypo/hyperthyroidism affecting ovulation.

Initial investigations (recommended after 12 months of trying, or 6 months if 35+, or immediately if obvious risk factors): Mid-luteal progesterone (day 21 in a 28-day cycle): level above 30 nmol/L confirms ovulation. If irregular cycles: timed to 7 days before next expected period. Semen analysis of partner (male factor must always be assessed concurrently). Assessment of ovarian reserve: anti-Mullerian hormone (AMH) — reflects ovarian reserve; antral follicle count (AFC) by transvaginal ultrasound; FSH and oestradiol (day 2-5 of cycle) — elevated FSH and low AMH indicate diminished reserve. Hormone profile: FSH, LH, oestradiol, thyroid function (TSH), prolactin (elevated in hyperprolactinaemia — pituitary adenoma), testosterone and DHEAS (elevated in PCOS/adrenal causes). Transvaginal ultrasound: assesses uterine cavity (fibroids, polyps, congenital anomalies), ovarian morphology (polycystic appearance in PCOS — 20+ follicles per ovary), and AFC. Hysterosalpingography (HSG): X-ray assessment of tubal patency and uterine cavity — first-line tubal imaging. Laparoscopy + dye test: gold standard for tubal patency and direct visualisation of pelvis for endometriosis, adhesions — more invasive, reserved for those with suspected pathology or failed initial treatment.

Ovulatory dysfunction: Clomifene citrate (50-150mg days 2-6) — anti-oestrogen, stimulates FSH release; 70-80% ovulation rate, 35-40% pregnancy rate; first-line for PCOS. Letrozole (aromatase inhibitor, 2.5-7.5mg days 2-6) — increasingly preferred over clomifene for PCOS (NEJM 2014 trial: higher live birth rate); reduces multiple pregnancy risk. Gonadotrophins (FSH injections — subcutaneous, 37.5-150 IU daily) with ultrasound monitoring: used for clomifene/letrozole-resistant PCOS and Group 1 hypothalamic failure; risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy requires careful monitoring. Dopamine agonists (cabergoline, bromocriptine) for hyperprolactinaemia — restores ovulation in 70-90%. Tubal disease: laparoscopic salpingolysis (adhesion division) and salpingostomy for mild/moderate tubal disease; hydrosalpinx requires salpingectomy before IVF (hydrosalpingeal fluid reduces IVF success by 50%). Endometriosis: laparoscopic excision/ablation of endometriosis improves natural fertility for Stage I-II; IVF for severe endometriosis. Intrauterine Insemination (IUI): prepared sperm inserted directly into the uterine cavity around ovulation — success rate approximately 10-15% per cycle; suitable for mild male factor, unexplained, or cervical factor infertility. IVF (In Vitro Fertilisation): stimulated oocyte retrieval, fertilisation in the laboratory, embryo culture, and embryo transfer — live birth rates 30-40% per cycle under 35, declining with age. Intracytoplasmic Sperm Injection (ICSI): injection of a single sperm into the oocyte — used for severe male factor. Oocyte donation: for POI and severely diminished ovarian reserve. Preimplantation Genetic Testing for Aneuploidy (PGT-A): screens embryos for chromosomal abnormalities before transfer.

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of fertility treatment — severe OHSS (ascites, pleural effusions, renal impairment, thrombosis) occurs in 0.2–2% of stimulated IVF cycles and requires hospitalisation; GnRH antagonist protocols with GnRH agonist trigger reduce OHSS risk significantly. Multiple pregnancy from gonadotrophin therapy or IVF without single embryo transfer increases risks of prematurity, low birth weight, neonatal ICU admission, and cerebral palsy — single embryo transfer is now standard practice in most countries. Ectopic pregnancy risk is elevated in women with tubal factor infertility undergoing IVF (1–3% of transfers); early transvaginal ultrasound at 6 weeks post-transfer is essential. Emotional and psychological consequences of infertility — depression, anxiety, grief, and relationship strain — are significant and frequently underrecognised; evidence-based psychological support should be integrated into infertility care pathways. Financial burden of repeated IVF cycles can be devastating. Cancer risk from fertility medications remains under long-term study; current evidence does not support a significantly elevated risk for breast, ovarian, or uterine cancers following IVF.

Optimise BMI before conception — both obesity (BMI above 30) and underweight (BMI below 18.5) impair ovulation and IVF outcomes. Quit smoking — smoking accelerates ovarian ageing and reduces IVF success by 30-50%. Limit alcohol — above 14 units/week reduces fertility. Reduce stress — chronic psychological stress impairs hypothalamic-pituitary-ovarian function. Take folic acid 400mcg daily from 3 months before conception (5mg if high-risk — diabetes, family history of NTD, BMI above 30). Screen and treat STIs (Chlamydia trachomatis) — the most preventable cause of tubal infertility; routine testing in all sexually active women under 25. Avoid unsafe abortions and unnecessary uterine instrumentation to prevent Asherman's syndrome. For women 35+: do not delay referral — fertility declines rapidly; seek specialist assessment after 6 months. Egg freezing (oocyte vitrification) offers fertility preservation for women planning to delay childbearing or undergoing gonadotoxic cancer treatment.

Seek specialist fertility assessment after 12 months of regular unprotected sex without conception if under 35, or after 6 months if aged 35 or above. Seek immediate assessment if you have: irregular or absent periods (suggesting ovulatory disorder), known previous pelvic infection or STI (risk of tubal damage), previous ectopic pregnancy, previous pelvic surgery, known endometriosis, premature menopause symptoms (hot flushes, vaginal dryness before 40), or known reproductive anatomy abnormality. Do not wait 12 months if you have any identifiable risk factor for reduced fertility. Both partners should be assessed together — male factor accounts for approximately 30-40% of infertility and semen analysis should be arranged at the outset.