What are the chances of success for a patient with Recurrent Pregnancy Loss (RPL), stage 4 endometriosis, and mild adenomyosis, using 5 Preimplantation Genetic Testing (PGT) tested embryos and 2 untested embryos, with Plaquenil (hydroxychloroquine), prednisone, possibly Intravenous Immunoglobulin (IVIG) and blood thinners, and undergoing a modified natural transfer?

Success Rates with PGT-Tested Embryos in RPL with Endometriosis and Adjuvant Immunotherapy

For a patient with RPL, stage 4 endometriosis, and mild adenomyosis using 5 PGT-tested embryos with the described immunomodulatory protocol, the cumulative live birth rate is approximately 60-70% across all transfers, with each individual PGT-tested embryo transfer offering roughly 50-60% success per attempt in optimal conditions.

Primary Success Determinant: Number of Previous Miscarriages

The most critical prognostic factor is your total number of prior pregnancy losses, not the endometriosis or adenomyosis 1:

• ≤4 previous miscarriages: Significantly better outcomes with adjusted odds ratio of 3.13 for achieving pregnancy beyond 12 weeks 1
• ≥5 previous miscarriages: Substantially reduced success rates, with only 18.8% live birth rate in untreated controls, though this improves to 66.7% with appropriate immunomodulation 2

Impact of PGT Testing on Your Specific Case

PGT-tested embryos dramatically improve your odds by eliminating chromosomal abnormalities as a cause of loss:

• Single euploid blastocyst transfer is strongly recommended regardless of your history, as this minimizes multiple pregnancy risks while maximizing per-transfer success 3, 4
• The 2 untested embryos carry significantly higher risk of aneuploidy-related loss and should only be used after exhausting PGT-tested options 4
• Even with low ovarian reserve concerns, PGT testing mitigates the increased aneuploidy risk that typically accompanies advanced reproductive age 4

Endometriosis and Adenomyosis Considerations

Stage 4 endometriosis and mild adenomyosis create an inflammatory uterine environment but do not preclude success with proper management:

• The ill-defined endometrial-myometrial junction often seen with adenomyosis has limited evidence regarding impact on outcomes, though endometrial thickness ≥7mm remains the practical target before transfer 3, 4
• Your modified natural cycle approach is appropriate, as it avoids the high estrogen exposure of stimulated cycles that could theoretically worsen endometriosis-related inflammation 5

Immunomodulatory Protocol Assessment

Hydroxychloroquine (Plaquenil)

Limited benefit for preventing early miscarriage in RPL patients 1:

• Recent 2024 prospective data from 100 pregnancies showed HCQ exposure did not prevent further miscarriages, with 62% still ending before 12 weeks 1
• The only predictor of success was number of previous losses, not autoantibody status 1
• However, if you have documented antiphospholipid antibodies meeting APS criteria, HCQ may provide additional benefit when combined with aspirin and heparin 5

Prednisone

Not recommended as routine therapy 5:

• The American College of Rheumatology strongly recommends against adding prednisone to standard therapy (aspirin + heparin) in patients where standard treatment has failed, as no controlled studies demonstrate benefit 5
• Prednisone should not be empirically increased during ART procedures 5

IVIG (Intravenous Immunoglobulin)

May be beneficial specifically for primary RPL with ≥5 previous losses 2:

• In patients with primary RPL (no prior live births) and ≥5 miscarriages, IVIG improved live birth rate from 18.8% to 66.7% (p=0.0113) 2
• For primary RPL with <5 miscarriages, benefit was not statistically significant (61.5% vs 49.3%, p=0.548) 2
• IVIG showed NO benefit for secondary RPL (prior live birth followed by losses): 33.3% vs 47% live birth rate (p=0.495) 2
• The American College of Rheumatology conditionally recommends against IVIG for refractory obstetric APS, as it has not been demonstrably helpful 5

Blood Thinners (Aspirin and Heparin)

Strongly recommended if you have documented antiphospholipid antibodies 5:

• For obstetric APS (≥3 losses <10 weeks, or loss ≥10 weeks, or preterm delivery <34 weeks due to preeclampsia/IUGR): Combined low-dose aspirin + prophylactic-dose LMWH is strongly recommended throughout pregnancy 5
• For positive antiphospholipid antibodies during ART procedures: Prophylactic anticoagulation with heparin or LMWH is conditionally recommended to prevent thrombosis during the transfer cycle 5
• For thrombotic APS: Therapeutic-dose LMWH + aspirin is strongly recommended 5
• Without documented antiphospholipid antibodies or APS criteria, routine anticoagulation is not recommended 5

Modified Natural Transfer Protocol Optimization

Your modified natural cycle approach is appropriate and should include 3:

• Endometrial thickness target ≥7mm before proceeding to trigger 3
• Single embryo transfer (SET) mandatory to minimize multiple pregnancy complications 3, 4
• Continue progesterone supplementation until 10 weeks gestation if pregnancy occurs 3
• If using estrogen supplementation, maintain for 3-4 weeks after positive pregnancy test, then taper over 2 weeks 3

Realistic Cumulative Success Projection

With 5 PGT-tested embryos transferred sequentially as single embryo transfers:

• If ≤4 previous miscarriages: Approximately 70-80% cumulative live birth rate across all 5 transfers
• If ≥5 previous miscarriages without IVIG: Approximately 50-60% cumulative live birth rate
• If ≥5 previous miscarriages with IVIG (primary RPL only): Approximately 65-75% cumulative live birth rate 2

Each individual transfer carries approximately 50-60% success rate per euploid embryo in optimal conditions, with success heavily dependent on your specific miscarriage history 1, 2.

Critical Caveats

Disease activity must be quiescent before proceeding 5:

• ART should be deferred if any rheumatic or autoimmune disease is moderately or severely active 5
• Six months of stable inactive or low-level disease is recommended before attempting transfer 5
• The thrombotic risk from elevated estrogen (even in modified natural cycles) necessitates medical clearance if you have any thrombotic history 5

The 2 untested embryos carry substantially higher failure risk and should be reserved as last resort options after the 5 PGT-tested embryos are exhausted 4.