Female Factor Infertility - Podcast Version 0:00 / 0:00 1x 0.25x 0.5x 0.75x 1x 1.25x 1.5x 1.75x 2x Female factor infertility is a common cause of subfertility, and may result from ovulatory dysfunction, tubal disease, uterine abnormalities or unexplained causes. In this article, we shall look at the causes, investigations and management of female factor infertility. Key Points Infertility affects approximately 15% of couples worldwide. Female factors account for one third of cases, while combined male and female factors contribute to a further one third.4,13 Ovulatory dysfunction is the most common cause.1 Refer to secondary care after 1 year (earlier if 35 years or older, or risk factors are present). Management requires a biopsychosocial approach.3 Clinical Context Infertility is a disease of the reproductive system, defined as the failure to achieve a pregnancy after 12 months of regular unprotected sexual intercourse.1 For patients aged 35 and older, investigations and treatment may be offered if they don’t conceive in 6 months. There is an age-related decline in ovarian reserve and fecundity, the biological capacity to conceive within a menstrual cycle.3 Infertility is common, with an estimated lifetime prevalence of 17.5% and period prevalence of 12.6%. Around 10% of women report using fertility services.4,5 Globally, female infertility cases rose by 84% between 1990 and 2021.14 Beyond its reproductive impact, infertility can profoundly impact mental health, relationships and identity. Risk Factors Age Oocyte quality and quantity decline with age, particularly after 32 years and rapidly after 37 years. Previous sexually transmitted infection (STI) Chlamydia and gonorrhoea – PID can cause tubal damage and adhesions. Previous Medical/Surgical History Autoimmune disease (e.g. SLE, antiphospholipid syndrome, thyroid dysfunction). Appendicitis +/- peritonitis. Prior pelvic surgery, e.g. myomectomy, can lead to adhesions. Drugs NSAIDs – inhibit ovulation. Chemotherapy/pelvic radiotherapy – can cause premature ovarian failure. Drugs that raise prolactin or suppress hypothalamic-pituitary function, including antipsychotics, metoclopramide, methyldopa and SSRIs. Recreational drugs. BMI <18.5 or >30 Low BMI – hypothalamic amenorrhoea. Obesity is associated with anovulation, PCOS and miscarriage. Smoking Including passive smoking. Alcohol Advise drinking less than 2 units of alcohol no more than twice a week. Occupational and Environmental Factors Psychosocial stress – may reduce libido and intercourse frequency. Infertility and depression are interlinked. Pesticides, nitrous oxide, heavy metals, solvents and formaldehydes. Pathophysiology Female factor infertility can be broadly divided into: Ovarian causes – diminished ovarian reserve and ovarian insufficiency2 Ovulatory dysfunction (WHO Groups I-III below) Tubal disease Uterine/peritoneal factors WHO Categories3 Group I Hypothalamic pituitary failure Functional hypothalamic amenorrhoea – excessive exercise, low BMI, stress. Hypogonadotrophic hypogonadism – Kallmann syndrome, pituitary damage. Reduced or absent FSH. Reduced or absent LH. Low oestradiol. Prolactin normal unless pituitary cause. Group II Hypothalamic-pituitary-ovarian dysfunction Predominantly PCOS Normal FSH. Raised or normal LH (raised LH:FSH ratio). Normal oestradiol. Raised androgens. Raised AMH. Group III Ovarian failure Primary ovarian insufficiency. Menopause. Gonadal dysgenesis. Post-chemotherapy/radiotherapy ovarian failure. Hypergonadotrophic hypogonadism. Raised FSH. Raised LH. Reduced oestradiol. Reduced AMH. Diminished ovarian reserve – reduced oocyte quantity or quality. Associated with age, ovarian surgery, chemotherapy, radiotherapy and autoimmune disease.3 Low AMH, low antral follicle count Raised FSH Normal or raised oestradiol Tubal Factor Infertility2,3 Untreated STIs Risk of tubal occlusion is 10% for initial episodes of salpingitis and doubled with subsequent infections Endometriosis Previous sterilisation Pelvic infection, including diverticulitis or appendicitis Uterine Abnormalities1,2,3 Congenital: Müllerian duct anomalies – uterine didelphys, bicornuate or unicornuate uterus, and septate uterus Acquired: Leiomyoma (fibroids) – may impact implantation Asherman’s syndrome (intrauterine adhesions) – from previous endometritis or dilation and curettage (D&C) Adenomyosis – reduced endometrial receptivity Peritoneal Factors Endometriosis – may cause anatomical obstruction of fallopian tubes or produce cytokines that might damage sperm and embryo Adhesions Unexplained infertility – diagnosed in 25% of couples, where investigations fail to identify any male or female barriers to conception. Clinical Features Important features in the history include: Advanced age (>35 years) Menstrual irregularity or amenorrhoea Long or irregular cycles suggest oligo-ovulation or anovulation Shortening cycles may suggest reduced ovarian reserve Previous STIs or pelvic inflammatory disease Pelvic pain, dysmenorrhoea or dyspareunia – endometriosis or pelvic adhesions Previous ectopic pregnancy Autoimmune diseases, e.g. SLE, IBD Prior chemotherapy, radiotherapy or gonadotoxic treatment Previous pelvic or abdominal surgery, e.g. appendicectomy Medication history: prescribed, over-the-counter and recreational drugs Social history: smoking, alcohol, occupational exposures and stress Examination findings: Extremes of BMI Galactorrhoea Signs of hyperandrogenism, e.g. hirsutism or acne Abdominal or bimanual findings such as fibroids, adnexal masses, tenderness, uterine immobility or abnormal uterine shape Primary infertility refers to difficulty achieving a pregnancy or live birth in a patient who has never previously conceived. Secondary infertility refers to difficulty achieving a pregnancy or live birth in a patient who has previously had a pregnancy or live birth. Investigations and Screening By TeachMeSeries Ltd (2026) Diagnostic pathway for female factor infertility, from primary care assessment through to secondary care investigations Ovulation assessment Mid-luteal phase serum progesterone – confirms ovulation Measured later in long or irregular cycles; repeat weekly if needed Low progesterone suggests anovulation, though thresholds vary Hormonal tests FSH and LH – useful in irregular cycles, suspected hypogonadotrophic hypogonadism or premature ovarian insufficiency Testosterone – if clinical features of PCOS or hyperandrogenism Anti-Müllerian hormone (AMH) – alongside antral follicle count, predicts ovarian response to assisted conception Prolactin – in an ovulatory disorder, galactorrhoea or suspected pituitary tumour Thyroid function tests – if thyroid disease suspected Screening Chlamydia testing – if positive, treat partners, contact trace and assess tubal patency Rubella status Cervical screening should be up to date Secondary Care Investigations Tubal Patency Investigations3 No pelvic comorbidities: Hysterosalpingogram (HSG) Hysterosalpingo-contrast Ultrasonography (HyCoSy) X-ray or fluoroscopic test. Uses radio-opaque iodinated dye via cervix. May cause cramping – NSAIDs to be taken beforehand. Performed in follicular phase. Chlamydia screening before uterine instrumentation. Transvaginal ultrasound. Echogenic contrast or foam via cervix. No ionising radiation or iodinated contrast. Higher sensitivity and specificity than HSG. Operator-dependent. Free spill of contrast suggests patent tubes. HSG is a reliable initial investigation for tubal occlusion. Free spill of contrast suggests patent tubes. HyCoSy is usually done in specialist fertility clinics. In suspected pelvic comorbidity, e.g. PID, previous ectopic pregnancy and endometriosis:1 Laparoscopy and dye – assesses tubal and pelvic disease Hysteroscopy – not routine, but used if a uterine or endometrial abnormality is suspected Surgical treatment can sometimes be performed at the same time Management General Measures: Optimise medical co-morbidities, e.g. diabetes, thyroid disease Smoking cessation BMI – target 18-25kg/m² Review prescribed, over-the-counter and recreational drugs Stress management – psychological intervention to lower emotional distress may be helpful Medical treatment: ovulation-inducing agents: Clomifene citrate – anti-oestrogen drug Letrozole – aromatase inhibitor that lowers oestrogen levels Gonadotrophins – used in clomifene-resistant anovulatory infertility Pulsatile gonadotrophin-releasing hormone (GnRH) Dopamine agonists – used in hyperprolactinaemia For anovulation in PCOS, letrozole is usually used for ovulation induction. Metformin may also be useful, especially with insulin resistance. Surgical Management: Tubal surgery for mild tubal disease – largely superseded by IVF, unless another indication, e.g. pelvic pain Tubal catheterisation or cannulation – for proximal tube obstruction Laparoscopic salpingectomy – for hydrosalpinges Ovarian drilling – PCOS resistant to ovulation induction Ablation or excision of endometriosis Ovarian cystectomy – for endometriomas Myomectomy or polypectomy – for fibroids/polyps Hysteroscopic metroplasty – correction of uterine septum Assisted Reproduction Techniques (ART):3 Intrauterine insemination (IUI) Sperm is inserted around ovulation, sometimes with ovulation induction Indications: donor sperm, male factor infertility, mild endometriosis or unexplained infertility In-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) Recommended when ovulation induction has failed or tubal disease is present ICSI is used for significant male factor infertility Oocyte donation, in conjunction with IVF, used in: Age-related poor ovarian reserve Premature ovarian insufficiency Gonadal dysgenesis, e.g. Turner syndrome High risk of transmitting a serious genetic disorder Surrogacy – considered when the uterus is absent/severely damaged or pregnancy would be hazardous, e.g. severe cardiac disease. Complications and Follow-up Ovarian Hyperstimulation Syndrome (OHSS)1,3 Potentially life-threatening complication of ovarian stimulation. Characterised by increased capillary permeability, leading to fluid shifts, particularly into the abdominal cavity. Symptoms: bloating, abdominal pain, nausea/vomiting, ascites, dehydration, thromboembolism, or breathlessness in severe cases. Monitoring with hormone measurements and ultrasound reduces risk. Procedure-related Risks3 Depending on the procedure, but may include: Infection Bleeding Pain Ovarian torsion Visceral injury, e.g. bowel perforation during oocyte retrieval Anaesthetic complications Clomifene-induced hypo-oestrogenism1,3 Clomifene can cause anti-oestrogenic effects: hot flushes, headaches and visual symptoms. May impair implantation or sperm transport. Pregnancy-related risks1,3 Ectopic pregnancy – higher with prior tubal factor infertility, prior pelvic surgery, multiple-embryo or fresh embryo transfer Multiple pregnancy – occurs in around 10% of clomifene cycles and up to 30% of gonadotrophin and IVF cycles. Risks can be reduced by close monitoring and transferring fewer embryos Small increased risk of postpartum haemorrhage (PPH), pregnancy-induced hypertension, pre-eclampsia, and gestational diabetes ART is associated with a slightly increased risk of ovarian cancer and congenital abnormalities compared with natural conception; however, evidence is limited. Equity, Safety and Professionalism Inequality in access to fertility treatment across the UK. NHS-funded IVF is commissioned locally by Integrated Care Boards, creating a ‘postcode lottery’ where eligibility depends on where a patient lives.6 Eligibility criteria may exclude some patients. Local policies vary by infertility duration, BMI, smoking, previous children and prior treatment.7 Prior to referral, some areas require 2 years of regular unprotected intercourse for heterosexual couples, or 6 cycles of artificial insemination for female same-sex couples.6 Safety counselling is essential. Patients should understand the risks of ovulation induction and assisted reproduction, including OHSS, multiple pregnancy, ectopic pregnancy, miscarriage, procedure-related complications and emotional distress.8 Additional fertility treatment add-ons. Some investigations and treatments are offered privately at significant cost despite limited evidence of effectiveness. Clinicians should discuss costs, evidence and uncertainty around treatment. The HFEA provides an evidence-rating system to help patients make informed decisions.9 Recent Changes and Controversies Updated NICE guidance. NICE NG257, published in March 2026, aims to standardise assessment and treatment for fertility problems and reduce variation.1 NG257 removed the previous recommendations on hypothalamic-pituitary-ovarian dysfunction (predominantly PCOS), as NICE is developing a dedicated PCOS guideline. Overseas treatment. Patients may seek overseas treatment for lower costs, shorter waits or unavailable treatments. Counselling should cover safety, regulation, embryo transfer practices, follow-up and how success rates are reported. The HFEA does not recommend overseas treatment, as it only regulates UK-licensed clinics.11 Access for LGBTQ+ and single patients. These groups face additional barriers, particularly around NHS funding criteria. Recent policy changes have addressed some discriminatory barriers, including ending additional screening requirements for female same-sex couples and allowing people with HIV and an undetectable viral load to donate eggs or sperm.6,7 Falling NHS-funded IVF. NHS-funded IVF accounted for 27% of IVF cycles in 2022, down from 40% in 2012.6 Storage of gametes and embryos. From 2022, eggs, sperm and embryos can be stored for 55 years. This improves flexibility but raises concerns about counselling, consent and long-term storage.10 Pre-implantation embryo testing and polygenic screening.12 Patients may seek external embryo screening scores to rank embryos by predicted traits, e.g. disease risk, height or IQ. Using such scores for embryo selection is illegal in UK clinics, but difficult to enforce as analysis is often done abroad. References 1. National Institute for Health and Care Excellence. Fertility problems: assessment and treatment. NG257. 2026. Available from: https://www.nice.org.uk/guidance/ng257 [Accessed 03 Jun 2026]. 2. National Institute for Health and Care Excellence. Infertility. Clinical Knowledge Summary. 2023. Available from: https://cks.nice.org.uk/topics/infertility/ [Accessed 03 Jun 2026]. 3. BMJ Best Practice. Infertility in women. London: BMJ Publishing Group; 2024. Available from: https://bestpractice.bmj.com/topics/en-gb/498 [Accessed 03 Jun 2026]. 4. World Health Organization. Infertility. Geneva: WHO; 2024. Available from: https://www.who.int/news-room/fact-sheets/detail/infertility [Accessed 03 Jun 2026]. 5. World Health Organization. Infertility prevalence estimates, 1990-2021. Geneva: WHO; 2023. Available from: https://iris.who.int/server/api/core/bitstreams/a22ced65-46b1-4482-bf85-058719fec649/content [Accessed 03 Jun 2026]. 6. Department of Health and Social Care. NHS-funded in vitro fertilisation (IVF) in England. 2023. Available from: https://www.gov.uk/government/publications/nhs-funded-ivf-in-england/nhs-funded-in-vitro-fertilisation-ivf-in-england [Accessed 03 Jun 2026]. 7. Department of Health and Social Care. IVF law change to benefit couples with fertility issues. 2022. Available from: https://www.gov.uk/government/news/ivf-law-change-to-benefit-couples-with-fertility-issues [Accessed 03 Jun 2026]. 8. Human Fertilisation and Embryology Authority. Risks of fertility treatment. 2024. Available from: https://www.hfea.gov.uk/treatments/explore-all-treatments/risks-of-fertility-treatment/ [Accessed 03 Jun 2026]. 9. Human Fertilisation and Embryology Authority. Explore all treatments. 2024. Available from: https://www.hfea.gov.uk/treatments/explore-all-treatments/ [Accessed 03 Jun 2026]. 10. Human Fertilisation and Embryology Authority. New law comes into force giving greater flexibility for fertility patients. 2022. Available from: https://www.hfea.gov.uk/about-us/news-and-press-releases/2022/new-law-comes-into-force-giving-greater-flexibility-for-fertility-patients/ [Accessed 03 Jun 2026]. 11. Human Fertilisation and Embryology Authority. Fertility treatment abroad. 2024. Available from: https://www.hfea.gov.uk/treatments/explore-all-treatments/fertility-treatment-abroad/ [Accessed 03 Jun 2026]. 12. Human Fertilisation and Embryology Authority. PGT-P is not lawful in the UK, is not supported by evidence and may reduce the chances of having a baby overall. 2023. Available from: https://www.hfea.gov.uk/about-us/our-blog/pgt-p-is-not-lawful-in-the-uk-is-not-supported-by-evidence-and-may-reduce-the-chances-of-having-a-baby-overall/ [Accessed 03 Jun 2026]. 13. Walker MH, Tobler KJ. Female Infertility. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556033/ [Accessed 03 Jun 2026]. 14. Liu J, Qin Y, Liu H, Liu Y, Yang Y, Ning Y, et al. Global, regional, and national burden of female infertility and trends from 1990 to 2021 with projections to 2050 based on the GBD 2021 analysis. Sci Rep. 2025;15:17559. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12092605/ [Accessed 03 Jun 2026]. Recommended Reading NICE Guideline (NG257) – Fertility problems: assessment and treatment NICE CKS – Infertility BMJ Best Practice – Infertility in Women Department of Health and Social Care – Guidance on NHS-funded in vitro fertilisation (IVF) in England Human Fertilisation and Embryology Authority (HFEA) Rate This Article