Infertility Diagnosis, Treatment, and Fertility Preservation

Coverage Summary

This policy section evaluates a range of advanced fertility diagnostics, adjunctive procedures, and fertility preservation methods. Coverage positions are mixed by intervention: established cryopreservation methods (sperm, mature oocytes, embryos) are recognized as medically necessary in appropriate clinical scenarios (including iatrogenic fertility risk), while many diagnostics and adjunctive procedures (for example, EmbryoGlue, HBA/PICSI, IVM, sperm function tests, ERA/pET, Cap-Score, and endometrial procedures) are classified as insufficient evidence/experimental or investigational. The policy is current and reflects a template update dated 01/01/2026 that archived prior versions.

Medical-Necessity Criteria — Evidence-Based Positions

Overall evidence is heterogeneous and often inconclusive: some interventions have mixed trial and meta-analysis results (for example, hyaluronic acid–enriched transfer media/EmbryoGlue with meta-analyses suggesting probable increases in live birth but individual RCTs showing no benefit), while many advanced diagnostics and adjuncts lack high-quality, consistent data to demonstrate improved live birth or pregnancy outcomes. Professional society guidance (ASRM, ASCO, AUA, NICE) is cited and generally endorses established cryopreservation methods but considers IVM experimental, advises against routine use of certain tests (e.g., inhibin B, post-coital testing), and emphasizes that several newer assays or procedures are not recommended for routine practice pending further evidence.

Study / Guideline	Key finding
Heymann 2022 Cochrane (HA in transfer media)	HA probably increases live birth rate RR 1.21 (95% CI 1.1-1.31); increases clinical pregnancy and multiple pregnancy rates.
Bhoi 2024 retrospective multicenter (EmbryoGlue)	Retrospective study reported higher live birth (60.6% vs 47.5%) and clinical pregnancy rates with EmbryoGlue; authors note retrospective design and need for RCTs.
Yung 2021 RCT (EmbryoGlue in FET)	Randomized double-blind trial found no improvement in live birth after FET with EmbryoGlue versus standard medium.
Miller 2019 (PICSI vs ICSI RCT)	PICSI did not increase term livebirth versus ICSI; a reduction in miscarriage was observed.
Zheng 2022 RCT (IVM vs IVF in PCOS)	IVM inferior to IVF for 6-month cumulative ongoing pregnancy rates (22.3% vs 50.6%); concluded IVM was inferior in this trial.
Vuong 2023 systematic review (IVM)	Systematic review found data insufficient to draw definitive conclusions comparing IVM and conventional stimulation; more trials needed.
Van Hoogenhuijze 2021 (SCRaTCH trial)	Endometrial scratch produced a small, uncertain increase in live birth; authors recommend not performed outside trials.
Lensen 2019 RCT (endometrial scratching)	No difference in live birth between scratching and control (26.1% vs 26.1%); no significant benefit.
Papanikolaou 2023 (endometrial scratching meta-analysis)	Meta-analysis of hysteroscopy with ES reported improved clinical pregnancy and live birth rates but limited by poor study quality and heterogeneity.
Lepine 2019 Cochrane (HBA)	Hyaluronic acid selected sperm may have little or no effect on live birth or clinical pregnancy but may reduce miscarriage; quality of evidence low.
ASRM/ASCO/NICE guideline summaries	Society guidelines note IVM is experimental (ASRM); recommend cryopreservation approaches for cancer patients and advise against routine use of some tests (e.g., post-coital, inhibin B).

Fertility Preservation for People with Cancer

Documentation Required

Assess suitability for oocyte/embryo cryopreservation

Document the patient’s suitability for oocyte or embryo cryopreservation in the medical record. Specifically record that the patient is clinically well enough to undergo ovarian stimulation and egg retrieval, that the procedure will not worsen their underlying condition, and that there is adequate time to perform cryopreservation prior to the start of cancer treatment.

Document fitness for ovarian stimulation and retrieval
Document that the procedure will not worsen the cancer or other condition
Document available time before initiating gonadotoxic therapy

Documentation Required

Offer sperm cryopreservation to males/adolescents at risk

Tests and Procedures Not Recommended / Routine

Rationale: many specialized tests lack validated predictive value, standardized assays, or consistent associations with improved clinical outcomes. Guideline statements from ASRM, AUA/ASRM and NICE advise against routine use of several of these tests (for example, inhibin B and post-coital cervical mucus testing) or classify them as experimental, reflecting the absence of sufficient high-quality evidence to support routine clinical adoption.

Regulatory and Informational Notes

Billing Rule

Do not rely on FDA status for coverage decisions

Do not base coverage decisions solely on FDA approval status. FDA approval and PMN listings are informational only; verify member-specific benefit terms, state/federal mandates, and plan documents when determining coverage eligibility.

FDA approval alone is not a basis for coverage
Check member-specific benefit plan documents and applicable mandates
Use FDA PMN and product code resources for informational reference only

Provider Actions & Documentation

Documentation Required

Experimental/Investigational Use Documentation

For procedures or tests described as experimental or investigational (e.g., IVM, HBA, ROS, Cap-Score, SPA, ERA, EmbryoGlue per this policy section), document the investigational status in the medical record. Ensure informed consent is obtained and documented, and record justification for use (for example, enrollment in an approved clinical trial or treatment at a specialized center).

State investigational/experimental status in the record
Document informed consent specific to investigational use
Document clinical rationale and, if applicable, clinical trial or specialized center participation

Denial Risk

Potential Denial for Insufficient Evidence Services

Definitions and Key Evidence

Glossary:

• EmbryoGlue: HA-enriched embryo transfer medium (high hyaluronan concentration and low recombinant human albumin).

• HBA / PICSI: Hyaluronan Binding Assay or physiological ICSI — sperm selection method based on hyaluronic acid binding.

• IVM: In vitro maturation of oocytes — maturation of immature oocytes in the laboratory without standard ovarian stimulation.

• ERA / pET: Endometrial Receptivity Analysis and personalized embryo transfer guided by ERA results.

• Cap-Score: Test measuring sperm capacitation (GM1 localization) to estimate probability of generating pregnancy (PGP).

• Vitrification: Rapid cryopreservation method preferred for oocytes and embryos when equipment and expertise are available (preferred over controlled-rate freezing).

Citation	Key finding
Heymann et al., Cochrane (2020/2022)	Adding hyaluronic acid to transfer media probably increases live birth (RR 1.21, 95% CI 1.1–1.31) and clinical pregnancy; may slightly decrease miscarriage; evidence low-to-moderate certainty.
Yung et al., 2021 RCT	Randomized double-blind trial found EmbryoGlue (0.5 mg/mL HA) did not improve live birth after frozen embryo transfer compared with standard medium.
Bhoi et al., 2024 (retrospective)	Retrospective multicenter study reported higher live birth and clinical pregnancy rates with EmbryoGlue versus conventional medium but noted limitations of retrospective design and need for RCT validation.
Miller et al., 2019 (HABSelect/PICSI RCT)	PICSI (hyaluronan-based sperm selection) did not increase term livebirth compared with standard ICSI; a reduction in miscarriage was observed.
Lepine et al., 2019 Cochrane (advanced sperm selection)	Evidence suggests HA-binding sperm selection may have little or no effect on live birth or clinical pregnancy; further high-quality trials required.
Zheng et al., 2022 RCT (IVM vs IVF)	In women with PCOS, IVM was inferior to standard IVF for 6-month cumulative ongoing pregnancy rates (22.3% vs 50.6%).
Vuong et al., 2023 systematic review (IVM)	Systematic review concluded data are insufficient for definitive conclusions comparing IVM and conventional stimulation; more RCTs needed.
Van Hoogenhuijze et al., 2021 (SCRaTCH)	Endometrial scratch showed small, uncertain increases in live birth; authors recommend not performing outside clinical trials.
Lensen et al., 2019 RCT (endometrial scratching)	Large RCT found no difference in live birth between endometrial scratching and control (26.1% vs 26.1%).
Sanyal et al., 2023 systematic review (sperm function tests)	Majority of advanced sperm function tests (ROS, acrosome reaction, capacitation, DNA fragmentation) lack sufficient high-quality evidence and standardized assays to support routine clinical utility.
Sharara/Schinfeld/Cap-Score studies (2018–2020)	Observational studies show Cap-Score may predict probability of pregnancy in IUI and identify impaired capacitation in men questioning fertility, but evidence is insufficient for routine use and further validation needed.
Lourenço/Chen meta-analyses (SDF) 2022–2023	Meta-analyses yield inconsistent associations between sperm DNA fragmentation and ART outcomes; overall insufficient evidence to recommend routine clinical use of SDF testing for management decisions.

Revision History

2026-01-01revisedLatest

Summary of Changes dated 01/01/2026 indicates template update and creation of a shared policy version to support application to Oxford plan membership; archived previous policy versions 2025T0270LL and INFERTILITY 008.21. Text: "Template Update: Created shared policy version to support application to Oxford plan membership and archived previous policy versions." (non-material).