Impact of different luteal phase support protocols in fresh embryo transfers on perinatal outcomes of singleton in vitro fertilization pregnancies: a three-decade experience

Abstract Study question How can stimulation of corpus luteum in the luteal phase with human chorionic gonadotropin (hCG) improve obstetric and perinatal outcomes? Summary answer There is currently no evidence that the use of hCG as an alternative treatment for luteal-phase support (LPS) improves obstetric and perinatal outcomes. What is known already There are different approaches for providing LPS, although none have shown differences in pregnancy rates. However, emerging evidence has also revealed the important role of corpus luteum in obstetric and perinatal outcomes after in vitro fertilization (IVF) (preeclampsia or intrauterine growth restriction, among others) in the production of progesterone (can be administered exogenously) as well as the secretion of multiple vasoactive active substances. Study design, size, duration We performed a retrospective, single centre study between 1991-2021. A total of 2592 singleton pregnancies were analysed after fresh embryo-transfer according to LPS. Participants/materials, setting, methods IVF singleton pregnancies were stratified into two cohorts according to the LPS protocol: 1) trigger with 5000 IU urinary hCG (U-hCG) and LPS protocol with progesterone 200 mg x3/day/vaginally beginning the day after oocyte retrieval and one u-hCG bolus of 2500 IU, the day and 3 days after oocyte retrieval; and 2) trigger with 250 µgr of recombinant hCG and LPS protocol with only progesterone (200 mg x3/day/ vaginally). Main results and the role of chance We compared the reproductive outcomes between cycles in cohort 1) n = 527 and cohort 2) n = 2065. The two cohorts were stratified and analysed in three groups according to maternal age to reduce possible bias: 35 years old or less, between 36 and 39 years old, and 40 or more years old. In cohort 1, all the cycles followed a long agonist GnRH protocol, while in cohort 2, 78.11% received an agonist GnRH protocol and 21.89 % a GnRH antagonist protocol. Recombinant gonadotropins for ovarian stimulation was administered in all cycles. We observed a greater number of eutocic deliveries, a lower number of instrumentalized births and a stable caesarean rate along the study period. There were no statistical differences between the two treatment groups regarding hypertensive pregnancy disorders, intrauterine growth restriction, small for gestational age or large for gestational age. Group 2 showed an apparent greater tendency, albeit not significant, to preeclampsia and a significant increase in very preterm birth. Emerging evidence has also revealed the important role of corpus luteum in obstetric and perinatal outcomes following IVF. Limitations, reasons for caution The large number of pregnancies evaluated is a clear strength of this study. This is the first series comparing different perinatal outcomes according to LPS. In contrast, the retrospective design and long time period involving changes in laboratory and patient profiles is a clear limitation. Wider implications of the findings The optimization of IVF treatments is especially important and is related to multiple factors, including the individualization of treatments to ensure the safety of IVF treatment as well as that of the pregnancies derived thereof. More studies on the different LPS protocols available are needed. Trial registration number not applicable