30%
of infertility cases labelled 'unexplained'
25%
of women have a shifted implantation window
DNA
sperm fragmentation not tested in standard semen analysis
8
commonly missed tests listed in this guide
What Hasn't Been Tested Yet
Standard fertility workup misses these commonly relevant investigations.
Sperm DNA fragmentation index
Standard semen analysis checks count, motility, and morphology — it does not assess DNA integrity. Sperm DNA fragmentation >25% is associated with fertilisation failure and early pregnancy loss even when standard parameters are normal.
Endometrial receptivity analysis (ERA)
The implantation window is assumed to be standard — but in 25–30% of women with recurrent implantation failure, the window is shifted by 12–24 hours. ERA personalises embryo transfer timing.
Uterine natural killer (NK) cell testing
Elevated uterine natural killer cell activity is associated with implantation failure and early pregnancy loss. Testing requires an endometrial biopsy and is not part of standard fertility workup.
Thrombophilia and clotting panel
Factor V Leiden, prothrombin gene mutation, MTHFR, and antiphospholipid antibodies can impair placental blood flow and cause early pregnancy loss — often missed in standard workup.
Thyroid antibodies (anti-TPO, anti-Tg)
Thyroid antibodies cause miscarriage risk even when TSH is normal. Standard fertility workup often checks TSH only — not antibodies.
Comprehensive immune panel
Elevated natural killer cells, altered T-regulatory cells, and cytokine profiles can create an immune environment hostile to implantation — not assessed in standard workup.
Detailed hormonal profiling
A single Day 2–3 FSH/LH/oestradiol panel misses subtle luteal phase defects, prolactin elevation, and DHEA-S excess that can impair fertility without causing obvious cycle irregularity.
Hysteroscopy
Ultrasound misses small polyps, fibroids, adhesions, and septae that can physically impair implantation. Hysteroscopy provides direct visualisation of the uterine cavity.
Optimisation While You Investigate
Oocyte Quality
- •CoQ10 (ubiquinol) 400–600 mg/day for 90 days
- •Melatonin 3 mg at night (antioxidant in follicular fluid)
- •Eliminate alcohol completely
- •Anti-inflammatory Mediterranean diet
Sperm Quality
- •Partner: CoQ10 400 mg/day for 90 days
- •Partner: Vitamin C 1000 mg + Vitamin E 400 IU/day
- •Partner: Zinc 15–25 mg/day
- •Partner: Eliminate alcohol and reduce heat exposure
Endometrial Receptivity
- •Vitamin D3 — target 100–150 nmol/L
- •Omega-3 DHA/EPA 2 g/day
- •Optimise thyroid function (TSH 0.5–2.5 mIU/L)
- •L-arginine 2–3 g/day if thin endometrium
Immune Environment
- •Discuss immune testing with specialist if >2 failed transfers
- •Vitamin D3 — immune modulating at 100–150 nmol/L
- •Omega-3 reduces NK cell activity
- •Intralipid or IVIG — discuss with specialist if NK cells elevated
Your Action Plan
Next Steps Checklist
0/17 completed
Tests to Request
Sperm DNA fragmentation index (partner)
Full thyroid panel: TSH + free T4 + free T3 + anti-TPO + anti-Tg antibodies
Thrombophilia screen: Factor V Leiden, MTHFR, antiphospholipid antibodies
Uterine NK cell testing if recurrent implantation failure
Hysteroscopy to exclude uterine cavity abnormalities
Comprehensive Day 2–3 hormone panel including DHEA-S and prolactin
Optimisation Protocol
Start CoQ10 (ubiquinol) 400–600 mg/day — both partners
Optimise Vitamin D — target 100–150 nmol/L
Adopt anti-inflammatory Mediterranean diet
Eliminate alcohol — both partners
Optimise sleep: 7–9 hours, consistent timing
Address psychological stress — HPA axis suppresses GnRH pulsatility
Advocating for Yourself
Ask your specialist: 'What tests haven't been done yet?'
Request a second opinion if you have had 2+ failed IVF cycles with unexplained outcome
Ask about ERA testing before your next transfer
Bring this guide to your appointment — use the uninvestigated list as a conversation starter
Consider a reproductive immunologist referral if standard workup is complete