Should we proceed with In Vitro Fertilization (IVF)?

Should We Proceed with IVF?

The decision to proceed with IVF depends critically on the clinical context: for women with chronic myeloid leukemia requiring fertility preservation, referral to an IVF center is recommended with TKI discontinuation prior to oocyte retrieval 1; for couples with unexplained infertility who are treatment-naive with good prognosis (>30% spontaneous pregnancy chance within 12 months), IVF should be deferred in favor of expectant management or IUI with ovarian stimulation for at least 3 cycles 1, 2.

Clinical Context Determines IVF Appropriateness

For Fertility Preservation (CML or Other Medical Indications)

• Women with CML should stop TKI therapy before attempting natural pregnancy or oocyte retrieval and be referred to an IVF center in coordination with their obstetrician 1
• The optimal timing of TKI discontinuation before IVF is unknown, but discontinuation is mandatory due to risks of miscarriage and fetal abnormalities 1
• Embryo cryopreservation is the most established fertility preservation method with high success rates in women under 40 years of age 2
• Oocyte cryopreservation is suitable for women without partners or those who prefer not to create embryos 2
• Ovarian tissue cryopreservation may be considered when time constraints prevent standard ovarian stimulation protocols 2

Critical barriers to consider: Lack of access to IVF centers, high costs potentially not covered by insurance, embryo/oocyte storage costs, need for multiple IVF cycles to obtain viable embryos, and requirement for family medical leave 1

For Unexplained Infertility (Treatment-Naive Couples)

• In couples with unexplained infertility and a prognosis of spontaneous pregnancy >30% within 12 months (Hunault score >30%), IVF should be postponed for at least 6 months 1
• For couples with unexplained infertility, prognosis <30%, and total motile sperm count (TMSC) >10 million, IUI with ovarian stimulation is the recommended first-line treatment over IVF 1, 2
• At least 3 cycles of IUI with ovarian stimulation should be attempted before progressing to IVF 1, 2, 3
• IVF becomes appropriate after failed IUI attempts or when IUI-eSET achieves ongoing pregnancy rates exceeding 38% 2

For Age-Related Considerations

• Immediate IVF may be considered as first-line treatment in women older than 38-40 years due to declining female fecundity 4
• Female age should guide decision-making as fecundity declines significantly with advancing age 4

For Male Factor Infertility

• For TMSC between 3-10 million, IUI in natural cycles may be considered first 3
• For TMSC <3 million or severe oligoasthenoteratozoospermia, IVF with ICSI is more cost-effective and appropriate as first-line treatment 2, 3
• Above a pre-wash TMSC of 3 million, conventional IVF is more cost-effective than ICSI 2

For Tubal Factor Infertility

• IVF is indicated as first-line treatment in cases of untreated bilateral tubal factor 4
• Single embryo transfer should be strongly considered to minimize ectopic pregnancy risk (up to 20-fold increase with multiple embryo transfer) in patients with tubal factor infertility 5

Risk-Benefit Analysis by Clinical Scenario

Higher Benefit Scenarios (Favor IVF)

• Individuals already utilizing IVF with preimplantation genetic testing (PGT) for other reasons may add additional testing with favorable risk-benefit ratio 1
• Severe male factor infertility requiring ICSI 3, 4
• Bilateral tubal disease 4
• Advanced maternal age (>38-40 years) 4
• Failed multiple IUI cycles (≥3 cycles) 1, 3

Lower Benefit Scenarios (Defer IVF)

• Treatment-naive couples with good prognosis unexplained infertility 1, 6
• Couples seeking IVF solely for polygenic risk score testing, where harm may exceed benefit 1
• Adequate TMSC (>10 million) with no other indications 1

Important Caveats

• IVF is invasive, expensive, and carries risks including multiple pregnancy (up to 36% depending on therapy) and ovarian hyperstimulation syndrome (1-5% of cycles) 4
• Three cycles of IUI with ovarian stimulation using low-dose gonadotropins with strict cancellation criteria have proven as successful as one cycle of IVF in well-designed studies 6
• IVF with elective single embryo transfer (eSET) is increasingly preferred to minimize multiple pregnancy rates while maintaining pregnancy rates exceeding 38% 2
• Success rates vary significantly by age, diagnosis, and embryo quality 2, 4
• ICSI may be associated with higher rates of major birth defects compared to unassisted conception, despite no evidence of increased congenital abnormalities 2