Researchers in a 2023 study performed a double-blinded, multicenter randomized controlled trial and found no improvement in live birth rates for women using prednisone vs placebo, while noting higher rates of biochemical pregnancy loss and preterm births.
The immune-regulating drug prednisone is often prescribed in cases of recurrent implantation failure (RIF), however it’s not clear if it improves pregnancy outcomes.
Sun et al. (2023) performed a double-blinded, multicenter randomized clinical trial (RCT) to investigate whether or not there was a benefit in using prednisone in RIF patients. The RCT involved 357 patients who received prednisone and 358 who received a placebo, and took place at 8 academic fertility centers in China.
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Study details
- RIF patients had two or more good quality embryo transfers without pregnancy.
- Patients were under 38 years old and had good quality embryos.
- Patients with known autoimmune diseases were excluded.
- 10 mg of prednisone was taken daily during endometrial preparation for FET and stopped at week 12 of pregnancy.
- The primary outcome measured was the live birth rate.
The patient baseline characteristics were similar between the prednisone vs placebo groups, in terms of age at retrieval (~31), BMI, previous failed transfers (~3), embryo stage transferred, and more.
A logistic regression model was used for statistical adjustment of age, BMI, number of failed embryo transfer cycles, stage of embryo transferred and study site.
Increase in biochemical pregnancy loss with prednisone, no change in live birth and other outcomes
In the intention-to-treat analysis, the live birth rate (primary outcome) for prednisone vs placebo was 37.8% vs 38.8% (relative ratio [95% CI]: 0.97 [0.81-1.17]), p=0.78). Note that the relative ratio statistically adjusts the data for age, BMI and other factors as indicated above, of which there was no difference.
There were also no differences in clinical pregnancy rates (45.1% vs 45.5%) or miscarriage rates (16.2% vs 14.1%), but there was an increase in biochemical pregnancy losses (17.3% vs 9.9%, relative ratio [95% CI]: 1.75 [1.03-2.99]). Note: this means that after statistical adjustment, there were 1.75 times more biochemical losses (75%) in patients who took prednisone vs placebo.)
The results were similar in the per-protocol analysis.
Increase in preterm births with prednisone, no change in other adverse maternal, fetal or neonatal events
The researchers compared a wide range of maternal, fetal and neonatal adverse events.
The only statistically significant difference found was an increase in preterm deliveries with prednisone (11.8% vs 5.5%, absolute difference [95% CI]: 6.3 [0.2-12.4]).
Below is a list of the outcomes they looked at.
- Maternal:
- Vaginal bleeding
- Hyperemesis gravidarum
- Ectopic pregnancy
- Infection (upper respiratory tract infection and tuberculosis)
- Gestational diabetes
- Preterm delivery
- Premature rupture of membrane
- Gestational hypertension
- Preeclampsia
- Anemia
- Placenta previa
- Placental abruption
- Threatened preterm delivery
- Cervical incompetence
- Postpartum hemorrhage
- Postpartum anemia
- Puerperal infection
- Fetal:
- Neonatal jaundice
- Neonatal hospitalization >3 days
- Congenital anomalies
- Neonatal infection
- Neonatal respiratory distress syndrome
- Neonatal death
- Low birth weight
- Very low birth weight
- Macrosomia
- Birth-weight percentile among singletons (<10th and >90th)
Subgroup analyses
The researchers reanalyzed the data to compare different subgroups to see if they could find any differences. Here they only looked at the pregnancy outcomes (live birth, clinical pregnancy, losses, etc.), and not the maternal or neonatal outcomes.
When looking only at cleavage stage or blastocyst stage embryo transfers, they found no differences in pregnancy outcomes.
They also looked at subgroups where the women had 2, 3, 4 or 5 or more failed transfers. They found an increase in biochemical losses in the group with 3 failed transfers, and an increase in hCG-positive pregnancy rates with prednisone in the 4 failed transfer group.
Next they did a subgroup analysis only for live birth rates:
- Age (≤30, 31-35, >35): no difference
- BMI (<18.5, 18.5-23.9, 24-27.9, ≥28): no difference.
- Previous number of egg retrievals (1 or ≥2): no difference.
- Autoantibodies (antinuclear antibody, anti-cardiolipin antibody, anti-double-stranded DNA antibody): no difference.
Conclusions
This study found no differences in pregnancy, live birth or miscarriages rates in women who used prednisone compared to placebo. Women who used prednisone had an increase in biochemical losses and preterm births.
Consistent with this study, a 2022 Cochrane review found no benefit in the use of corticosteroids for live birth, pregnancy and miscarriage rates.
A limitation of this study is that only the 10 mg dose of prednisone was analyzed, and other doses may have different outcomes. Additionally, besides having RIF, the patients in this study had a relatively good prognosis and had good quality embryos available for transfer.
The authors also point to the larger problem of IVF add-ons and warn that they shouldn’t be used without adequate researcher using high quality RCTs.
Reference
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About Embryoman
Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.
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