What precautions should be taken for a patient with a family history of bipolar disorder, currently taking 450 mg of lithium, undergoing In Vitro Fertilization (IVF) with embryo freezing, regarding the effects of lithium on a potential fetus?

Lithium Management During IVF with Embryo Freezing

For a patient taking lithium 450 mg daily undergoing IVF with embryo freezing, lithium should ideally be discontinued or switched to an alternative mood stabilizer before conception attempts, but if discontinuation risks severe maternal psychiatric decompensation, continue lithium with intensive fetal monitoring and dose adjustments throughout pregnancy. 1

Critical Teratogenic Risk Assessment

Cardiac Malformations - The Primary Concern

• Ebstein's anomaly risk exists specifically during weeks 2-6 post-conception (the period of cardiac organogenesis), which is the critical window when lithium exposure poses the greatest teratogenic threat 1, 2
• The FDA drug label explicitly warns that "data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein's anomaly" 1
• However, more recent prospective studies (296 liveborn infants) demonstrated no increase in overall congenital anomaly rates, though 2 cases of Ebstein's anomaly occurred, and the absolute risk appears lower than initially reported in retrospective registries 3
• The teratogenic risk of lithium has been overestimated in the past based on flawed retrospective registry data, with prospective studies showing more reassuring outcomes 3, 4

Second and Third Trimester Complications

• Fetal/neonatal complications occur if lithium is taken during the second and third trimesters, including altered renal and endocrine function 2
• Lithium crosses the placenta and may cause fetal polyuria leading to polyhydramnios through a nephrogenic diabetes insipidus-like mechanism 5
• Neonatal lithium toxicity can occur in the peripartum period if maternal doses are not reduced 2

Pre-Conception Decision Algorithm

Option 1: Discontinue Lithium Before Conception (Preferred When Feasible)

• If possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother 1
• The best case scenario is to counsel women requiring lithium to plan pregnancy, allowing for temporary change in treatment regimen during embryogenesis 2
• Taper lithium gradually over 2-4 weeks minimum before attempting conception to minimize rebound mania risk, which exceeds 90% with abrupt discontinuation 6
• Withdrawal of maintenance lithium therapy is associated with dramatically increased relapse risk, especially within 6 months following discontinuation 6

Option 2: Switch to Alternative Mood Stabilizer

• Lamotrigine appears to be a possible alternative with a more favorable reproductive safety profile 3
• Valproate should be avoided due to higher teratogenic risk than lithium, particularly neural tube defects 7
• Atypical antipsychotics (aripiprazole, quetiapine) may be considered, though they carry metabolic risks 6

Option 3: Continue Lithium with Enhanced Monitoring (When Discontinuation Endangers Mother)

• When caring for a pregnant bipolar woman, physicians must consider both the risk of fetal exposure to mood stabilizers AND the risk of relapse if treatment is interrupted 4
• This option is appropriate when the patient has severe, treatment-resistant bipolar disorder with history of multiple hospitalizations, suicide attempts, or rapid relapse upon lithium discontinuation 6

IVF-Specific Timing Considerations

During Ovarian Stimulation and Egg Retrieval

• Lithium can be continued during ovarian stimulation and egg retrieval phases, as these occur before conception 2
• Maintain therapeutic lithium monitoring (levels 0.8-1.2 mEq/L) during this phase 6

Embryo Freezing Strategy

• Embryo freezing provides a critical advantage: it allows time to optimize the psychiatric medication regimen before embryo transfer 2
• Use the interval between egg retrieval and planned embryo transfer to either discontinue lithium or switch to a safer alternative 4
• This approach minimizes the risk of unplanned lithium exposure during the critical 2-6 week post-conception window 1, 2

If Lithium is Continued Through Pregnancy

First Trimester Management

• Fetal echocardiography should be performed to exclude cardiac anomalies, typically at 16-18 weeks gestation 3, 4
• High-resolution ultrasound at 18-20 weeks can detect Ebstein's anomaly and other cardiac defects 4
• Consider level II ultrasound for detailed fetal anatomic survey 2

Second and Third Trimester Adjustments

• Lithium requirements usually increase in the third trimester due to increased glomerular filtration rate and expanded volume of distribution 2
• Monitor lithium levels monthly during second trimester, then every 2 weeks during third trimester 2, 4
• Monitor for fetal polyhydramnios with serial ultrasounds, as lithium may cause fetal polyuria 5
• Assess fetal renal and thyroid function through ultrasound parameters 2

Peripartum Period - Critical Dose Reduction

• Lithium should be decreased in the peripartum period to avoid drug toxicity in the neonate and mother 2
• Reduce lithium dose by 30-50% at onset of labor or 24-48 hours before planned delivery 4
• Resume pre-pregnancy dose immediately postpartum to prevent postpartum relapse 4

Baseline Monitoring Requirements

• Before any pregnancy attempt, obtain baseline complete blood count, thyroid function tests, urinalysis, BUN, creatinine, serum calcium, and current lithium level 6, 8
• The American Academy of Child and Adolescent Psychiatry emphasizes that lithium should only be used where close clinical and laboratory monitoring are available 8

Common Pitfalls to Avoid

• Never discontinue lithium abruptly - this dramatically increases rebound mania risk and may precipitate severe psychiatric decompensation requiring hospitalization 6
• Do not assume lithium is absolutely contraindicated - the teratogenic risk has been overestimated, and for some women, continuing lithium represents the safest option when balanced against maternal psychiatric risks 3, 4
• Avoid switching to valproate as an alternative, as it carries higher teratogenic risk than lithium, particularly for neural tube defects 7
• Do not fail to reduce lithium dose peripartum - maintaining full therapeutic doses through delivery significantly increases neonatal toxicity risk 2
• Never use efavirenz, ribavirin, statins, or warfarin in women at risk for pregnancy, as these are potential teratogens 7

Risk-Benefit Communication

• The patient should be apprised of the potential risk to the fetus if she becomes pregnant while taking lithium 1
• Provide realistic risk/benefit assessment: the absolute risk of Ebstein's anomaly is approximately 0.05-0.1% (compared to 0.005% baseline), representing a 10-20 fold relative increase but still affecting fewer than 1 in 1000 exposed pregnancies 3
• Discuss that untreated bipolar disorder during pregnancy carries significant maternal and fetal risks, including poor prenatal care, substance abuse, suicide, and postpartum psychosis 9