Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial

Abstract

In vitro fertilization (IVF) cycles generate abnormalities in luteal-phase sex steroid concentrations and this represent an important limiting factor to achieve a good pregnancy rate. Although there are evidences about the usefulness of luteal phase support (LPS) after IVF cycles, no consensus exist about the best dose and way of progesterone (PG) administration, the advantages of estradiol (E2) supplementation and which IVF protocol could benefit from one more than other LPS scheme. Aim of the study was to assess the best LPS (low-dose PG, high-dose PG, high-dose PG and E2 supplementation) to achieve the highest clinical/ongoing pregnancy rate according to stimulation protocol, E2 at ovulation induction, endometrial thickness at pick-up and women’s age. We conducted a randomized trial on 360 women undergoing IVF (180 treated by long-GnRH agonist, 90 by short-GnRH agonist and 90 by short-GnRH antagonist protocol) and stimulated by recombinant follicle-stimulating hormone alone. Our data demonstrated that high-dose PG is better than low-dose to increase both clinical and ongoing pregnancy rate. E2 supplementation are mandatory in case of short-GnRH antagonist protocol and strongly suggested in all protocols when E2_max <5 nmol/l and endometrial thickness <10 mm. In long-GnRH agonist protocols, as well as in patients >35 years, the real advantages of E2 supplementation remain debatable and require further confirmation.

Chinese abstract

在体外受精（IVF）周期中黄体期的性激素浓度会产生异常，这是获得高妊娠率的一个重要的限制因素。尽管证据表明IVF周期后的黄体支持（LPS）是有益的，但在给予孕酮（PG）的最佳剂量和给药方式，补充雌二醇（E2）的优点，以及哪种IVF方案会比其它LPS方案获得更多益处等方面，尚未达成一致意见。本研究旨在依据促排卵方案、诱发排卵时的E2浓度、取卵时的子宫内膜厚度以及患者年龄，评估可获得最高临床/继续妊娠率的最佳LPS（低剂量PG，高剂量PG，高剂量PG加补充E2）。我们对360名正在进行IVF的女性（180名进行长GnRH激动剂方案，90名给予短GnRH激动剂方案，90名给予短GnRH拮抗剂方案）实施了随机试验，仅用重组卵泡刺激素促排卵。数据显示，高剂量PG比低剂量PG更能提高临床妊娠率和继续妊娠率。短GnRH拮抗剂方案必须补充E2，在所有方案中当E2_max＜5nmol/l和子宫内膜厚度＜10mm时强烈建议补充E2。对于长GnRH激动剂方案以及年龄＞35岁的患者，补充E2是否真正有益仍有争议，且需要进一步证实。

• Endometrium
• estradiol
• GnRH agonist
• GnRH antagonist
• IVF protocol
• luteal phase support
• pregnancy rate
• progesterone

Acknowledgements

The authors acknowledge Dr Stefano Gava, Dr Capuzzo Denise, Dr Elena Poli and Dr Manfè Serena, for the precious collaboration in patients recruitment and data collection. The authors acknowledge also the biologist team (Dr Maria Lia Coronella, Dr Cecilia Zicchina and Dr Alessandra Oliva) for the daily collaboration in the patient’s treatment.