Factors Linked to Ectopic Pregnancy in Women Undergoing IVF/ICSI Treatment

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Factors Linked to Ectopic Pregnancy in Women Undergoing IVF/ICSI Treatment

Ectopic pregnancy (EP)—when a fertilized egg implants outside the uterus, most often in the fallopian tubes—is a life-threatening first-trimester complication affecting 1.6% to 8.6% of women using assisted reproductive technology (ART) like in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). That’s more than four times the rate in natural pregnancies. While EP is a well-known risk in ART, the exact factors driving it remain unclear. A 2020 study from Zhejiang University’s Sir Run Run Shaw Hospital aimed to identify these factors to help reduce risk for patients.

What the Study Examined

The retrospective study analyzed 13,142 ART cycles (IVF/ICSI) that resulted in pregnancy between January 2013 and December 2017. Researchers compared women who had an EP (including heterotopic pregnancy, where both intrauterine and ectopic pregnancies occur) to those who had a healthy intrauterine pregnancy. Key factors evaluated included:

  • Age
  • Infertility type (primary: never pregnant; secondary: prior pregnancy)
  • Tubal factor infertility (scarred, blocked, or swollen fallopian tubes; prior EP or tube removal)
  • Embryo stage at transfer (cleavage-stage: day 3; blastocyst: day 5)
  • Cycle type (fresh vs. frozen-thawed embryo transfer)
  • Number of embryos transferred (1–3)
  • Endometrial combined thickness (ECT: uterine lining thickness measured by ultrasound)
  • Prior history of EP

Key Definitions

To ensure consistency, the study followed guidelines from the Society for Assisted Reproductive Technology:

  • Intrauterine pregnancy: A gestational sac seen on ultrasound or confirmed by birth, spontaneous abortion, or therapeutic abortion.
  • Biochemical pregnancy: Positive pregnancy test but no visible sac or clinical pregnancy.
  • Ectopic pregnancy: Gestational sac outside the uterus (e.g., fallopian tubes, ovaries).
  • Heterotopic pregnancy: Coexistence of intrauterine and ectopic pregnancies.

Critical Results

Of the 13,142 pregnancies, 2.12% (278) were EP, and 0.27% (35) were heterotopic. The most impactful findings:

  1. Tubal factor infertility is the strongest risk factor: Women with tubal damage (e.g., blockages, hydrosalpinx, prior EP) were 4 times more likely to have an EP than those without (adjusted odds ratio [OR]: 3.995). Damaged tubes can trap embryos or disrupt their journey to the uterus.

  2. Blastocyst transfer reduces risk—especially for those with prior EP: Women who received a blastocyst (day 5) transfer had a lower EP rate than those who received a cleavage-stage (day 3) transfer (8.6% vs. 15.6% in non-EP group). For patients with 1–4 prior EPs, the gap was even larger: only 7.8% of EP cases had blastocyst transfer, compared to 22.4% of non-EP cases.

  3. Thinner uterine lining increases risk: Women with an ECT under 9mm had a 59.4% EP rate—significantly higher than the 47.5% rate in non-EP patients. A thin lining may reduce uterine receptivity, pushing embryos to implant outside the uterus.

  4. Prior EP boosts repeat risk: Women with 1–4 prior EPs had a higher chance of repeat EP, likely due to lasting tubal damage from previous ectopic pregnancies.

Why This Matters for Patients and Clinicians

  • Tubal factor infertility: If you have blocked or scarred tubes, your doctor may recommend salpingectomy (tube removal) before ART to lower EP risk.
  • Blastocyst transfer: For women with prior EP, blastocyst transfer is strongly advised. Blastocysts are more mature and less likely to be displaced into the fallopian tubes by uterine contractions.
  • Endometrial health: A thick, healthy lining is key for implantation. Your doctor may monitor ECT and suggest treatments (e.g., estrogen) to improve it.
  • Embryo number: Transferring 1–2 embryos (not 3) aligns with safety guidelines and may reduce EP risk (though the study found no statistically significant link here).

Study Limitations

The research was retrospective (using past records), so recall bias is possible. It also focused on one Chinese center with a high rate of tubal disease—results may differ in other populations. Additionally, prior EP is grouped with tubal infertility, making it hard to separate their effects.

Final Recommendations

For women undergoing IVF/ICSI:

  • If you have tubal issues or prior EP: Ask about blastocyst transfer—this simple change could cut your EP risk.
  • Optimize your lining: Work with your doctor to improve endometrial thickness before transfer.
  • Limit embryos: Stick to 1–2 embryos to align with safety standards.

This study, published in the Chinese Medical Journal (2020) by Xiao-Ying Jin, Song-Ying Zhang, and colleagues from Zhejiang University’s Sir Run Run Shaw Hospital, provides actionable insights to reduce EP risk in ART. While more research is needed, these findings offer clear steps to make assisted reproduction safer.

doi:10.1097/CM9.0000000000001058

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