P-396 Comparison of luteal support protocols in fresh IVF/ICSI cycles: A network meta-analysis
Authors:   K. Specialty Registrar Obstetrics & Gynaecology
Published: July 2024

Abstract

Study question
What is the optimal LPS in fresh cycles in agonist and antagonist cycles?

Summary answer
Vaginal progesterone, with the addition of SCGnRH-a results in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.

What is known already
Despite the proven superiority of various Luteal Phase Support protocols (LPS) over placebo in view of improved pregnancy rates in fresh cycles of IVF (in vitro fertilization) and ICSI (intracytoplasmic sperm injection) cycles, there is ongoing controversy over specific LPS protocol selection, dosage, and duration.

Study design, size, duration
Network Meta-analysis. Twelve databases, namely Embase (OVID), MEDLINE (R) (OVID), GlobalHealth (Archive), GlobalHealth, Health and Psychosocial Instruments, Maternity & Infant Care Database (MIDIRS), APA PsycTests, ClinicalTrials.gov, HMIC Health Management Information Consortium, CENTRAL, Web of Science, Scopus and two prospective registers, MedRxiv, Research Square were searched from inception to Aug.1st, 2023.The study was prospectively registered under the PROSPERO database.

Participants/materials, setting, methods
Only RCTs were included. Primary outcomes included clinical pregnancy and live birth events, while secondary outcomes included biochemical pregnancy, miscarriage, multiple pregnancy and OHSS events. Bayesian network meta-analysis (NMA) model was employed for outcome analysis, presenting fixed effects, odds ratios (ORs) with 95% credibility intervals (CrIs). Vaginal Progesterone (VP) was considered the reference LPS for the purposes of the NMA given its’ clinical relevance.

Main results and the role of chance
Seventy-six RCTs, comparing 22 interventions, and including 26536 participants were included in the present NMA.Combinatorial regimens, with subcutaneous GnRH-a (SCGnRH-a) on a vaginal progesterone base and oral oestrogen (OE) appeared to overall improve clinical pregnancy events; VP+OE+SCGnRH-a [OR 1.57 (95% CrI 1.11 to 2.22)], VP+SCGnRH-a [OR 1.28 (95% CrI 1.05 to 1.55)] as well as live pregnancy events, VP+OE+SCGnRH-a [OR 8.81 (95% CrI 2.35 to 39.1)], VP+SCGnRH-a [OR 1.76 (95% CrI 1.45 to 2.15)]. Equally, the progesterone free LPS, intramuscular human chorionic gonadotrophin, [OR 9.67 (95%CrI 2.34, 73.2)] was also found to increase live birth events, however was also associated with an increased probability of ovarian hyperstimulation, [OR 1.64 (95%CrI 0.75, 3.71)]. Of all LPS protocols, VP+SC GnRH-a was found to significantly reduce miscarriage events, OR 0.54 (95% CrI 0.37 to 0.80). Subgroup analysis according to ovarian stimulation (OS) protocol revealed that the optimal LPS across both long and short OS, taking into account increase in live birth and reduction in miscarriage as well as OHSS events, was VP+SCGnRH-a, with an OR 2.89 [95%CrI 1.08, 2.96] and OR 2.84 [95%CrI 1.35, 6.26] respectively.

Limitations, reasons for caution
Given the anticipated diversity of measured outcomes, a Bayesian meta-synthesis approach has been adopted to account for the expected heterogeneity and to incorporate modelling flexibility by allowing for posterior distributions interpreted as SUCRA probabilities with the later enabling crisper communication of the uncertainty in the treatment effects estimates.

Wider implications of the findings
Overall, NMA data suggest that combinatorial treatments, with the addition of SCGnRH-a on a VP base result in improved clinical pregnancy and live birth events in both GnRH-agonist and antagonist ovarian stimulation protocols.

Trial registration number
Not applicable