Overview

Unexplained infertility is diagnosed when a couple has not conceived after 12 months of regular unprotected intercourse, and a full fertility evaluation finds no apparent cause. It affects 25–30% of couples undergoing investigations. "Unexplained" does not mean hopeless — with the right treatments, most couples go on to conceive.

Possible Underlying Causes (Still Being Researched)

• Subtle egg quality issues not visible on standard assessment
• High sperm DNA fragmentation — not assessed by routine semen analysis
• Embryo developmental problems detectable only in the IVF lab
• Subtle endometrial receptivity issues
• Immunological factors at the embryo-endometrial interface
• Early or microscopic endometriosis not detected on imaging

Diagnosis (Exclusion of All Standard Causes)

• Semen analysis (WHO 2021)
• Ovarian reserve — AMH, AFC, Day 3 FSH
• Ovulation confirmation — mid-luteal progesterone
• Tubal patency — HSG or HyCoSy
• Uterine cavity — 3D ultrasound or SIS
• Thyroid function and prolactin

Extended Investigations

• Sperm DNA fragmentation testing
• ERA (Endometrial Receptivity Analysis)
• Laparoscopy — to exclude early endometriosis

Treatment

• Watchful waiting — for women under 35 with short duration of infertility
• Ovarian stimulation with IUI — 3–4 cycles before escalating
• IVF — most effective; also serves a diagnostic function, revealing fertilisation and embryo development issues
• IVF with ICSI — when high SDF or previous poor fertilisation
• PGT-A — to select chromosomally normal embryos
• ERA — personalised embryo transfer timing

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