Fresh vs Frozen Embryo Transfer after GnRH-a Long Protocol

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Fresh vs frozen embryo transfer after GnRH-a long protocol

Fertility outcomes in women after controlled ovarian stimulation with gonadotropin releasing hormone agonist long protocol: fresh versus frozen embryo transfer

A retrospective cohort study was conducted to compare live birth rates, in women undergoing fresh and frozen embryo transfer, following the commonly used gonadotropin releasing hormone agonist (GnRH-a) long protocol for ovarian stimulation during IVF.

For this study women who visited the Chongqing Reproductive and Genetics Institute between 2016 to 2018 were evaluated against a strict inclusion / exclusion criteria. Only women undergoing their very first IVF cycle, with the GnRH-a protocol followed by day 3 twin embryo transfer (ET) were included, while the exclusion criteria ruled out: women > 34 years old; less than 2 embryos available; day 3 endometrium thickness < 0.7cm; day 5 transfers or PGT cycles; chromosome or uterine abnormality.

In this clinic GnRH-a long protocol began with GnRH-a administration, during the mid-luteal phase, in the previous menstrual cycle. After 14 to 18 days depending on hormone levels, 75 to 300 IU daily of recombinant follicle stimulating hormone (rFSH) was added until induction of ovulation. Once a follicle reached 18µm in diameter, recombinant human chorionic gonadotropin (rHCG) was injected and oocytes retrieved 36 hours later.

In the fresh embryo transfer group, luteal support began immediately after retrieval with 2 good or excellent quality embryos transferred on day 3. Similarly in the frozen embryo transfer group, luteal support commenced 3 days before transfer, using either an artificial or natural cycle to prepare the endometrium. In both groups however, luteal support continued until week 12 of gestation.

Overall 7814 women met the inclusion/exclusion criteria, with 5216 fresh ET and 2598 frozen ET cycles part of the final analysis. Baseline characteristics showed some initial differences between the 2 groups, with age, duration of infertility and basal FSH being statistically higher in the fresh ET group. On the other hand, AMH, primary cause of infertility and proportion of nulliparous women was significantly lower in the fresh ET group.

This resulted in a total gonadotropin dose that was statistically higher in the fresh ET group, with lower estradiol levels on hCG trigger day, and significantly less number of oocytes retrieved (10.49 vs. 17.97), culminating in less available embryos for transfer (4.00 vs 5.44) in the fresh ET group .

After clinical outcomes were adjusted for potential confounders (age, infertility duration, BMI, AMH, oocytes retrieved and available embryos) multivariate logistic regression analysis found no significant difference between fresh and frozen ET groups with regards to clinical pregnancy rate (65.8% vs. 66.9%), ectopic pregnancy rate and pregnancy loss rate.

However implantation (48.6% vs 47.0%) and live birth rates (57.1% vs 54.8%) were statistically higher in the fresh ET group, even though baseline characteristics of this group were more unfavorable, suggesting the recent freeze all strategy is not for everyone.


SUMMARY: IS IT BETTER TO DO A FRESH OR FROZEN EMBRYO TRANSFER

In this large retrospective study, comparing fresh vs frozen embryo transfer among infertile women, who underwent the gonadotropin releasing hormone agonist (GnRH-a) long protocol, fresh embryo transfer resulted in a statistically significant higher live birth rate (57.1% vs 54.8%, p = 0.012).


Limitations

  1. Retrospective analysis
  2. Baseline characteristics between the 2 groups significantly different


Similar studies

Roque M, et al. (2019). Fresh versus elective frozen embryo transfer in IVF/ICSI cycles: a systematic review and meta-analysis of reproductive outcomes. https://doi.org/10.1093/humupd/dmy033

Shi Y, et al. (2018). Transfer of Fresh versus Frozen Embryos in Ovulatory Women. https://doi.org/10.1056/NEJMoa1705334

Vuong L N, et al. (2018). IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries. https://doi.org/10.1056/NEJMoa1703768


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