Fertility Problems: Assessment and Treatment

Note on renumbering: NICE guideline CG156 "Fertility problems: assessment and treatment" (published 2013, updated 2017) has been withdrawn and replaced by NG257, published 31 March 2026. Content below reflects NG257. Where NG257 explicitly removed or deferred a topic to another guideline, this is flagged.

Key Recommendations

• Offer initial investigations to couples who have not conceived after 1 year of regular unprotected vaginal intercourse
• If using artificial insemination, offer investigation if not conceived after 6 cycles of insemination
• Refer/investigate earlier (at presentation, without waiting) if: age ≥36, either partner has a suspected/known clinical cause of infertility, or a history of predisposing factors
• Fertility declines with age: most significant after 35, accelerates after 38
• Both partners should be investigated simultaneously

Initial Assessment

Female Investigations

• History: menstrual cycle regularity, duration of infertility, previous pregnancies, STI history, cervical surgery, medical/surgical history
• Hormonal profile (day 2–5): FSH, LH, oestradiol, prolactin, thyroid function — used alongside age as predictors of ovarian reserve and response to stimulation
• Anti-Müllerian hormone (AMH): marker of ovarian reserve (does not predict egg quality)
• Day 21 progesterone (or 7 days before expected period, adjusted for cycle length): a level of ≥30 nmol/L indicates likely ovulation
• Pelvic ultrasound: assess ovarian morphology (antral follicle count), uterine anatomy, exclude pathology
• Tubal patency: hysterosalpingography (HSG), hysterosalpingo-contrast sonography (HyCoSy), or diagnostic laparoscopy, depending on risk factors for tubal/pelvic pathology
• Rubella immunity: check and vaccinate if non-immune (advise contraception for 1 month post-vaccination)

Male Investigations

• Semen analysis: at least one sample (if abnormal, repeat to confirm)
• WHO reference values (5th centile, as used in NG257):
  • Volume: ≥1.4 ml
  • Concentration: ≥16 million/ml
  • Progressive motility: ≥30%
  • Normal morphology: ≥4%
• If azoospermic: further investigation (FSH, testosterone, karyotype as indicated); refer to andrology. Obstructive azoospermia → surgical correction or sperm retrieval; non-obstructive azoospermia → surgical sperm retrieval (micro-TESE may be considered). Surgical sperm retrieval is not offered where Y-chromosome AZFa/AZFb microdeletions are identified.

Ovulation Induction (Anovulatory Infertility)

Important change: NG257 removed its recommendations on hypothalamic–pituitary–ovarian dysfunction (predominantly PCOS-related anovulation), stating NICE is developing a separate PCOS guideline. NICE NG257 therefore no longer makes a formal recommendation on letrozole vs clomifene for PCOS. Until the dedicated PCOS guideline is published, the ESHRE International PCOS Guideline (2023, amended 2025) remains the standard clinical reference and continues to recommend letrozole as first-line ovulation induction agent for PCOS-related anovulation (higher live birth rate than clomifene), with clomifene citrate as an alternative and gonadotrophins as a further option requiring intensive ultrasound monitoring. For MRCOG purposes, be aware this content currently sits outside NICE NG257's active recommendations.

• Hypogonadotropic hypogonadism (non-PCOS anovulation) remains covered directly by NG257: offer gonadotrophins with LH activity, or GnRH, to induce ovulation.
• OHSS remains a key risk of any gonadotrophin-stimulated ovulation induction (see OHSS section below).

Intrauterine Insemination (IUI)

NG257 narrows IUI eligibility compared with the previous CG156 recommendations:

• Unstimulated IUI, up to 12 cycles: offered to people unable to have vaginal intercourse because of physical disability or psychosexual problems, and to those using donor sperm due to male-partner azoospermia
• Unstimulated donor IUI, up to 6 cycles: offered to those using donor insemination with no known clinical causes of infertility
• Unexplained infertility: consider up to 4 cycles of IUI with ovarian stimulation using gonadotrophins before proceeding to IVF, once the couple has been trying to conceive for a total of 2 years; ovarian stimulation as a stand-alone treatment (without IUI) is not recommended
• IUI should not be used ahead of IVF where a clinical cause of infertility is suspected or confirmed

IVF / ICSI

NHS/NICE Access Criteria (NG257)

• Eligible if: diagnosed infertility unsuitable for other treatment, OR unexplained infertility after 2 years of regular unprotected vaginal intercourse, OR failure to conceive after 12 cycles of artificial insemination (of which 6 or more are IUI)
• Upper age limit for access: under 42
• Under 40: offer 3 full cycles of IVF; if unsuccessful, consider up to 3 further full cycles (up to 6 total), all to complete before the 40th birthday
• Age 40–41: offer 1 full cycle if no previous IVF cycle, no evidence of low ovarian reserve, and implications of treatment at this age have been discussed
• Ovarian reserve and previous self-funded cycles must be discussed/counted as part of eligibility assessment

ICSI Indications

• Severe male factor (severe oligospermia, obstructive or non-obstructive azoospermia with surgical sperm retrieval)
• Previous poor fertilisation with IVF
• Using frozen or surgically retrieved sperm

Ovarian Hyperstimulation Syndrome (OHSS)

• Risk factors: young age, low BMI, PCOS, high AMH, high antral follicle count, previous OHSS
• Mild: abdominal bloating, mild pain
• Moderate: nausea, vomiting, USS evidence of ascites, enlarged ovaries
• Severe: tense ascites, oliguria, haemoconcentration, thromboembolism, pleural effusion, ARDS
• NG257 requires clinics providing gonadotrophin stimulation to have protocols for preventing, diagnosing and managing OHSS, but defers detailed OHSS-prevention technique recommendations to the ESHRE guideline on ovarian stimulation for IVF/ICSI (2025 update) rather than specifying them itself. In practice this still means: GnRH antagonist protocol, GnRH agonist trigger, "freeze all" strategy, and cabergoline remain the standard prevention strategies.

Lifestyle Modifications

• BMI: women with BMI ≥30 kg/m² are likely to take longer to conceive (and, if anovulatory, weight loss is likely to increase conception chance); BMI <18.5 kg/m² with irregular/absent periods — increasing weight is likely to improve conception chance
• Smoking: cessation advised — reduces fertility in women; associated with reduced semen quality in men
• Alcohol: no more than 1–2 units, once or twice per week, is safer than higher intake for women trying to conceive; full abstinence is the safest approach. For men, up to 14 units/week is unlikely to affect semen quality
• Caffeine: NG257 states there is no consistent evidence of an association between caffeinated drinks and fertility problems (a change in framing from the previous "limit to 200mg/day" pregnancy-safety advice)
• Folic acid: standard preconception dosing (400mcg daily; higher dose for raised BMI or other risk factors) is covered under NICE's maternal and child nutrition guidance, not restated in detail within NG257 itself

Important Facts for MRCOG

• CG156 has been replaced by NG257 (March 2026) — know this renumbering for exam purposes
• Investigate after 1 year (or immediately/at presentation if ≥36 or known risk factors)
• Day 21 progesterone ≥30 nmol/L indicates likely ovulation
• AMH: marker of ovarian reserve (NOT egg quality)
• WHO semen analysis reference values: concentration ≥16 million/ml, progressive motility ≥30%, morphology ≥4%
• PCOS/anovulation ovulation-induction recommendations are no longer part of active NICE guidance — NICE removed them from NG257 pending a dedicated PCOS guideline; letrozole-first-line remains standard per ESHRE, but do not cite it as a current NICE NG257 recommendation
• IUI eligibility narrowed under NG257: largely reserved for those unable to have intercourse, donor-sperm/donor-insemination scenarios, and stimulated IUI (4 cycles) before IVF in unexplained infertility — no longer a blanket "6 cycles unstimulated IUI" offer for mild male factor
• NICE (NG257): up to 6 full IVF cycles may be considered for women <40 (3 initially, up to 3 more if unsuccessful); 1 cycle for ages 40–41; access capped under age 42
• ICSI: for severe male factor
• OHSS: most serious complication of ovarian stimulation; NG257 now points to the ESHRE guideline for detailed prevention protocols

Source: NICE NG257 (replaces CG156, archived 2026 — CG156 itself was last updated 2017) (March 2026 (NG257 published 31 March 2026); verified 2026-07-17)

Read the original on nice.org.uk

Clinically reviewed by NHS obstetricians and gynaecologists · Source last updated March 2026 (NG257 published 31 March 2026); verified 2026-07-17

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