What are the risks of transferring two embryos in the next IVF (In Vitro Fertilization) cycle after a previous twin demise at 16 weeks with a history of complicated pregnancy and chorioamnionitis (inflammation of the chorion and amnion membranes)?

Strongly Recommend Single Embryo Transfer (SET) in the Next IVF Cycle

Given the patient's history of twin demise at 16 weeks with chorioamnionitis, transferring two embryos again poses unacceptably high risks of recurrent multiple pregnancy complications, and elective single embryo transfer (eSET) should be strongly recommended for the next cycle. 1

Evidence-Based Rationale

No Clinical Factor Justifies Double Embryo Transfer

The 2024 ESHRE guidelines explicitly state that no clinical or embryological factor per se justifies a recommendation of double embryo transfer (DET) instead of eSET in IVF/ICSI 1. This includes:

• Previous pregnancy loss does not justify DET - The decision to perform DET should not be based on previous pregnancies or live births from ART 1
• Number of failed cycles does not justify DET - Previous unsuccessful ART treatments should not determine embryo transfer number 1
• Duration of infertility does not justify DET - This factor alone should not guide the decision toward DET 1

Comparable Live Birth Rates with Repeated SET

The cumulative live birth rate after repeated SET (one fresh cycle followed by one frozen cycle) is equivalent to a single cycle of DET 1, 2, 3. Specifically:

• When comparing one cycle of DET versus repeated SET, there is no significant difference in cumulative live birth rates (OR 1.22,95% CI 0.92-1.62) 2
• For a woman with a 40% chance of live birth following DET, the chance following repeated SET would be between 30% and 42% 2
• Subsequent transfer of a single frozen embryo achieves live birth rates comparable with DET 3

Dramatically Reduced Multiple Pregnancy Risk

The multiple pregnancy rate is 30-fold higher with DET compared to repeated SET 1, 2. The evidence shows:

• Multiple pregnancy rate with DET versus repeated SET: OR 30.54 (95% CI 7.46-124.95) 2
• For a woman with 15% risk of multiple pregnancy following DET, the risk following repeated SET would be between 0% and 2% 2
• DET carries an 8-fold higher risk of multiple pregnancy compared to single-cycle SET (OR 8.47,95% CI 4.97-14.43) 2

Specific Risks Relevant to This Patient

Given the history of twin demise with chorioamnionitis, the following risks are particularly concerning with DET:

Pregnancy Complications:

• Pre-eclampsia, gestational diabetes, and emergency cesarean section rates are all elevated with multiple pregnancies 1
• Preterm labor risk is substantially increased 1
• Even singleton pregnancies after DET carry higher risks of neonatal death and complications compared to SET 1

Ectopic Pregnancy Risk:

• Risk increases up to 20-fold with the number of embryos transferred 1
• Risk is elevated after transfer of two versus one embryo regardless of developmental stage or freezing status 1

Monozygotic Twinning:

• If transferring blastocysts, there is higher monozygotic twin potential, creating twin risk even with SET 1
• Blastocysts should be transferred as SET because of high risk of multiple pregnancy complications 1

Recommended Transfer Strategy

For Women Under 38 Years with Good Prognosis

Transfer one cleavage-stage embryo in the fresh cycle, followed by one blastocyst-stage embryo in the subsequent frozen-thawed cycle 4. This strategy:

• Increases live birth rates compared to fresh cleavage-stage DET (44.8% vs 34.5%, adjusted OR 1.63) 4
• Decreases multiple live birth rates 4
• Reduces preterm birth rate (adjusted OR 0.64) 4
• Maintains similar neonatal birth weight for singletons 4

For Women 38 Years or Older or with Only Two Embryos

Transfer one embryo per cycle, but the beneficial effect on live birth rates may be less pronounced 4. However, the reduction in multiple pregnancy complications still strongly favors SET 1.

Critical Counseling Points

The patient must understand:

• Medical risks: Short- and long-term complications of multiple pregnancy including preterm birth, low birthweight, maternal morbidity, and neonatal complications 1
• Psychological burden: Exhaustion, psychological strain, and family stress associated with multiple births 1
• Financial implications: Increased healthcare costs and financial burden from multiple pregnancy complications 1
• Success rates: Cumulative live birth rates with repeated SET are equivalent to DET while avoiding twin risks 2, 3

Common Pitfalls to Avoid

• Do not assume previous pregnancy loss indicates need for DET - This is explicitly not a justification for transferring multiple embryos 1
• Do not transfer two blastocysts - The high implantation rate and monozygotic twinning risk make this particularly dangerous 1
• Do not consider fetal reduction as a backup plan - Transfer of two or more embryos with intention of fetal reduction is not recommended 1
• Do not transfer more than two embryos under any circumstances - This dramatically increases higher-order multiple pregnancy risk 1